Carbon Nanoparticle-Loaded Iron [CNSI-Fe(II)] in the Treatment of Advanced Solid Tumor

Brief summary public domain (ClinicalTrials.gov)

This Phase I clinical trial aims to evaluate the safety, tolerability, pharmacokinetics (PK) profile and preliminary efficacy of intratumoral injection of Carbon Nanoparticle-Loaded Iron \[CNSI-Fe(II)\] in patients with advanced solid tumors. The study also aims to observe dose-limiting toxicities (DLT) of CNSI-Fe(II) to determine the maximum tolerated dose (MTD) or the highest injectable dose in humans, providing dosing guidelines for future clinical studies. CNSI-Fe(II) shows promise as an innovative tumor therapeutic agent due to its unique properties of ferroptosis. The study primarily focuses on assessing the potential efficacy of CNSI-Fe(II) in patients with advanced solid tumors, particularly in patients with Kras mutation, e.g., pancreatic cancer patients.

Detailed description public domain (ClinicalTrials.gov)

Indications: This study targets patients with advanced solid tumors who have either failed standard treatments (progression or intolerance) or lack available standard treatment options. Common tumor types include colorectal, pancreatic, breast, gastric, cervical, lung, head and neck, and prostate cancers. Objectives: The primary goal is to assess the safety and tolerability of intratumoral injections of Carbon Nanoparticle Loaded Iron \[CNSI-Fe(II)\] in advanced solid tumor patients. This involves identifying dose-limiting toxicities (DLT) and determining the maximum tolerated dose (MTD) or highest injectable dose for subsequent clinical dosing decisions. Secondary objectives include evaluating the pharmacokinetics (PK) of CNSI-Fe(II) and its preliminary efficacy. Exploratory objectives is to understand the pharmacodynamics (PD) of CNSI-Fe(II), exploring the relationship between tumor size, injection dose, and drug concentration. Participants: Up to 30 subjects will participate across 3 to 6 centers, with the final number dependent on dose group evaluations and tolerability. Exit Criteria: Subjects may be withdrawn by researchers if they deviate from the protocol, impacting safety or efficacy assessment. Subjects can also voluntarily withdraw per guidelines, and their reasons will be documented. Efforts will be made to complete assessments for withdrawn cases. Dose Selection: Based on animal toxicology and effective dose data, a starting dose of 0.5 mg/kg (escalating to 30 mg, 60 mg and 90 mg) is selected. Adjustments may occur if DLT is observed or MTD is not reached. As of March 28, 2024, only one case of DLT occurred in the 90 mg dose group among the 30 mg, 60 mg, and 90 mg dose groups, demonstrating favorable safety and tolerability. The study has successfully passed the SRC meeting, allowing for further dose exploration at 120 mg, 150 mg, and potentially higher doses. Therefore, this protocol is hereby revised. Study Design: This open-label Phase I trial assesses CNSI-Fe(II) intratumoral injections in advanced solid tumor patients. The study includes screening, treatment (with DLT evaluation), and follow-up phases. Dose Escalation: The "3+3 method" guides dose escalation. Enrollment occurs in dose groups; dose escalation decisions are based on DLT occurrence. DLT Evaluation: DLTs are defined using toxicity criteria, assessed during the first cycle (21 days). Escalation decisions depend on DLT occurrence. DLT is defined as toxicities that are considered definitely or possibly related to the investigational drug CNSI-Fe(II) and occur within the first cycle (21 days) after the first dose. This includes Grade 4 hematological toxicity, Grade 3 hematological toxicity lasting \>7 days after optimal treatment, Grade 3 thrombocytopenia with bleeding or requiring platelet transfusion, and Grade 3 neutropenia with fever. Non-hematological toxicity: 1. Grade 3 cardiac toxicity lasting more than 3 days after optimal treatment or Grade 4 cardiac toxicity. 2. Grade 3 liver toxicity (for subjects with liver or bone metastasis and baseline liver enzyme ALT, AST, or ALP at Grade 2, ALT, AST, or ALP \>10×ULN) lasting more than 3 days after optimal treatment or Grade 4 liver toxicity. 3. Any Grade 3 non-hematological toxicity (excluding laboratory abnormalities) lasting more than 7 days after optimal treatment, except for Grade 3 nausea, Grade 3 vomiting, or Grade 3 diarrhea. 4. Any Grade 4 non-hematological toxicity (excluding laboratory abnormalities). 5. Any Grade 3 or 4 non-hematological laboratory abnormality if it requires medical intervention, leads to hospitalization, or persists at Grade 3 or above for 7 days or more after discontinuation of the drug. Other: 1. Any Grade 5 toxicity. 2. Other toxicities requiring early termination of CNSI-Fe(II) treatment as decided by the investigator and sponsor.

Detailed description public domain (ClinicalTrials.gov)

Besides evaluating the safety and tolerability of CNSI-Fe(II), this study will also preliminarily assess the efficacy of CNSI-Fe(II) in patients with advanced solid tumors. The investigator will evaluate CNSI-Fe(II)'s efficacy based on imaging examinations (computed tomography \[CT\], positron emission tomography \[PET\]/CT, or magnetic resonance imaging \[MRI\]), following the revised RECIST v1.1 criteria. Baseline imaging evaluations will be conducted within 28 days before the first treatment in the study. Subsequent tumor assessments will be performed for all subjects in the study at weeks 3-4 and, for those entering the maintenance phase, at weeks 7-8. Confirmation will be required for subjects achieving a complete response (CR) or partial response (PR) at least 4 weeks after the initial response. Baseline evaluations must include chest, abdomen, pelvis, skull (to exclude brain metastases), and other suspected tumor sites. Subsequent evaluations should reassess all measurable and evaluable lesions identified at baseline, including chest, abdomen, pelvis, and other suspected tumor sites. The imaging methods used for efficacy evaluation during the study must be consistent with the baseline imaging evaluation. Medicinal Products: The study uses CNSI-Fe(II) consisting of a nanoparticle carbon dispersion injection and injectable ferrous sulfate. Preparation of CNSI-Fe(II): Take one vial of injectable ferrous sulfate, keeping the aluminum cap and rubber stopper tightly closed and removing only the plastic outer cap of the aluminum-plastic combination cap. Slowly draw an appropriate amount of nanoparticle carbon dispersion injection using a suitable syringe and inject it into the vial containing ferrous sulfate, ensuring the solution is thoroughly mixed. The preparation of CNSI-Fe(II) should be done under aseptic conditions, avoiding exposure to air. It should be prepared and used at room temperature within 6 hours. Dosing: Dosing varies per phase and dose group, ensuring administration within the target tumor. PK and PD Analysis: Concentration-time curves, AUC, Cmax, Tmax, and PD marker levels are assessed using descriptive statistics. Statistical Analysis: Descriptive statistics are employed for demographic, safety, efficacy, and PK/PD data. No formal hypothesis testing is planned. Study Duration: The study will continue from the approval of the study by the Ethics Committee (EC) until the expected sample size is reached, subject to actual circumstances. The study is anticipated to end 28 days after the last subject has received a maximum of two doses of the study drug. After the study is completed, subjects who continue to achieve Complete Response (CR) or Partial Response (PR) and are determined by the investigator to still benefit from the treatment can continue to receive the study drug as a gift until disease progression, intolerable toxicity, or the investigator determines it is not appropriate to continue the study drug or the sponsor terminates the study.

Intervention public domain (ClinicalTrials.gov)

Drug: CNSI-Fe(II) 30 mg. The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion.

Intervention public domain (ClinicalTrials.gov)

Drug: CNSI-Fe(II) 60 mg. The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion.

Intervention public domain (ClinicalTrials.gov)

Drug: CNSI-Fe(II) 90 mg. The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion.

Intervention public domain (ClinicalTrials.gov)

Drug: CNSI-Fe(II) 120 mg. The dosing regimen is the same as that for the 30 mg, 60 mg, and 90 mg dose groups. Additionally, if a single lesion cannot accommodate the full corresponding dose of the investigational drug, additional lesions may be selected for simultaneous injection. When multiple lesions are injected, the drug distribution should be allocated proportionally according to the size of each lesion or determined based on the investigator's assessment of an appropriate distribution.

Intervention public domain (ClinicalTrials.gov)

Drug: CNSI-Fe(II) 150 mg. The dosing regimen is the same as that for the 30 mg, 60 mg, and 90 mg dose groups. Additionally, if a single lesion cannot accommodate the full corresponding dose of the investigational drug, additional lesions may be selected for simultaneous injection. When multiple lesions are injected, the drug distribution should be allocated proportionally according to the size of each lesion or determined based on the investigator's assessment of an appropriate distribution.

Arm public domain (ClinicalTrials.gov)

CNSI-Fe(II) 30 mg (experimental): 30 mg CNSI-Fe(II) 30 mg: The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion.

Arm public domain (ClinicalTrials.gov)

CNSI-Fe(II) 60 mg (experimental): 60 mg CNSI-Fe(II) 60 mg: The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an dditional dose may be administered based aon the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion.

Arm public domain (ClinicalTrials.gov)

CNSI-Fe(II) 90 mg (experimental): 90 mg CNSI-Fe(II) 90 mg: The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion.

Arm public domain (ClinicalTrials.gov)

CNSI-Fe(II) 120 mg (experimental): 120 mg CNSI-Fe(II) 120 mg: The dosing regimen is the same as that for the 30 mg, 60 mg, and 90 mg dose groups. Additionally, if a single lesion cannot accommodate the full corresponding dose of the investigational drug, additional lesions may be selected for simultaneous injection. When multiple lesions are injected, the drug distribution should be allocated proportionally according to the size of each lesion or determined based on the investigator's assessment of an appropriate distribution.

Arm public domain (ClinicalTrials.gov)

CNSI-Fe(II) 150 mg (experimental): 150 mg CNSI-Fe(II) 150 mg: The dosing regimen is the same as that for the 30 mg, 60 mg, and 90 mg dose groups. Additionally, if a single lesion cannot accommodate the full corresponding dose of the investigational drug, additional lesions may be selected for simultaneous injection. When multiple lesions are injected, the drug distribution should be allocated proportionally according to the size of each lesion or determined based on the investigator's assessment of an appropriate distribution.

Primary outcome public domain (ClinicalTrials.gov)

Safety and Tolerability Assessment of CNSI-Fe(II). This primary outcome measure is centered on the assessment of CNSI-Fe(II)'s safety and tolerability throughout the study. It encompasses the following assessments: Dose-Limiting Toxicity (DLT): This assessment involves the ongoing monitoring of adverse events, with a focus on determining their nature, severity, and frequency. Adverse events will be systematically categorized and reported according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Maximum Tolerated Dose (MTD): The MTD is a critical outcome measure representing the highest injectable dose in humans that can be safely administered without causing excessive adverse effects. The determination of MTD will be based on the careful observation and analysis of DLT data. The MTD was not determined in this Phase I study, and the MAD is 150mg. Units of Measure: DLT: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0. MTD: Milligrams (mg) of CNSI-Fe(II). Time frame: 21 days.

Secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Cmax (ng/mL) Profile Assessment of CNSI-Fe(II) of First Dosage. Time frame: 72 h.

Secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Tmax (h) Profile Assessment of CNSI-Fe(II) of First Dosage. Time frame: 72 h.

Secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: AUC (ng•h/mL) Profile Assessment of CNSI-Fe(II) of First Dosage. Time frame: 72 h.

Secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: t1/2 (h) Profile Assessment of CNSI-Fe(II) of First Dosage. Time frame: 72 h.

Secondary outcome public domain (ClinicalTrials.gov)

Evaluated as CR (Complete Response) in the Preliminary Efficacy Assessment.. Time frame: Observation period for a single dose is 21~28 days, the observation period for two doses is doubled..

Secondary outcome public domain (ClinicalTrials.gov)

Evaluated as PR (Partial Response) in the Preliminary Efficacy Assessment.. Time frame: Observation period for a single dose is 21~28 days, the observation period for two doses is doubled..

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * Patients must meet all of the following criteria to be eligible: 1. Understand and voluntarily sign the informed consent form (ICF), demonstrating willingness and ability to comply with all trial requirements. 2. Male or female aged 18-80 years (inclusive) at the time of signing the ICF. 3. Histologically or cytologically confirmed advanced solid tumors with ineffective current standard therapy (disease progression after treatment or intolerable treatment) or lack of effective standard treatment options. Eligible tumor types include colorectal cancer, pancreatic cancer, breast cancer, gastric cancer, cervical cancer, lung cancer, head and neck cancer, bile duct cancer, kidney cancer, prostate cancer, vulvar cancer, etc. Note: Patients with advanced solid tumors experiencing disease progression due to the inability to receive standard treatment for any reason or those with tumor types insensitive to existing standard treatments (e.g., pancreatic cancer, undifferentiated thyroid cancer, and sarcomas) after receiving first-line standard treatment are also eligible. 4. Presence of at least one measurable lesion according to RECIST v1.1, which has not received radiation (except for lesions showing clear progression after radiation) or tissue biopsy within 7 days before the first dose. 5. Lesions amenable to injection, either directly or with assistance from medical imaging. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 7 days before the first dose. 7. Expected survival of ≥12 weeks. 8. Adverse drug reactions (ADR) caused by previous treatments have recovered to Grade 1 or lower (except for alopecia) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 before screening. 9. Left ventricular ejection fraction (LVEF) ≥50%. 10. Within 7 days prior to the first dose, have adequate hematologic and end-organ function, with laboratory tests meeting the following criteria: 1. Hematology No use of granulocyte colony-stimulating factor (G-CSF) within 14 days prior to hematology laboratory tests, and absolute neutrophil count (ANC) ≥1.5×109/L; No platelet transfusion within 14 days prior to hematology laboratory tests, and platelet count (PLT) ≥90×109/L; No blood transfusion or use of erythropoietin within 14 days prior to hematology laboratory tests, and hemoglobin (Hb) ≥90 g/L; 2. Renal function Serum creatinine (Cr) ≤1.5×upper limit of normal (ULN) or calculated …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 19 participants (actual).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Safety and Tolerability Assessment of CNSI-Fe(II) [21 days]. Count Of Participants, Participants. Number of patients with DLT: CNSI-Fe(II) 30 mg (n=3): 0; CNSI-Fe(II) 60 mg (n=3): 0; CNSI-Fe(II) 90 mg (n=6): 1; CNSI-Fe(II) 120 mg (n=3): 0; CNSI-Fe(II) 150 mg (n=3): 0. Number of patients who did not reach DLT: CNSI-Fe(II) 30 mg (n=3): 3; CNSI-Fe(II) 60 mg (n=3): 3; CNSI-Fe(II) 90 mg (n=6): 5; CNSI-Fe(II) 120 mg (n=3): 3; CNSI-Fe(II) 150 mg (n=3): 3.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Cmax (ng/mL) Profile Assessment of CNSI-Fe(II) of First Dosage [72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 6903.00 (6200.77); CNSI-Fe(II) 60 mg (n=4): 6982.50 (3547.65); CNSI-Fe(II) 90 mg (n=6): 3520.33 (3610.57); CNSI-Fe(II) 120 mg (n=3): 8626.67 (10698.73); CNSI-Fe(II) 150 mg (n=3): 13961.67 (17868.76).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Tmax (h) Profile Assessment of CNSI-Fe(II) of First Dosage [72 h]. Mean, time (h) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 0.15 (0.08); CNSI-Fe(II) 60 mg (n=4): 0.41 (0.43); CNSI-Fe(II) 90 mg (n=6): 0.33 (0.31); CNSI-Fe(II) 120 mg (n=3): 0.18 (0.09); CNSI-Fe(II) 150 mg (n=3): 0.20 (0.06).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: AUC (ng•h/mL) Profile Assessment of CNSI-Fe(II) of First Dosage [72 h]. Mean, h*ng/mL (Standard Deviation). AUC(0 ~ 72 h): CNSI-Fe(II) 30 mg (n=3): 16748.60 (9698.84); CNSI-Fe(II) 60 mg (n=4): 25231.99 (7924.80); CNSI-Fe(II) 90 mg (n=6): 13664.73 (9241.15); CNSI-Fe(II) 120 mg (n=3): 36728.03 (48218.01); CNSI-Fe(II) 150 mg (n=3): 64118.50 (77650.64). AUC (0 ~ ∞): CNSI-Fe(II) 30 mg (n=3): 17715.81 (9468.52); CNSI-Fe(II) 60 mg (n=4): 30514.46 (13955.09); CNSI-Fe(II) 90 mg (n=6): 18430.79 (12946.52); CNSI-Fe(II) 120 mg (n=3): 41790.83 (49972.22); CNSI-Fe(II) 150 mg (n=3): 67276.22 (75429.26).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: t1/2 (h) Profile Assessment of CNSI-Fe(II) of First Dosage [72 h]. Mean, time (h) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 1.96 (0.92); CNSI-Fe(II) 60 mg (n=4): 4.28 (1.80); CNSI-Fe(II) 90 mg (n=6): 3.04 (2.04); CNSI-Fe(II) 120 mg (n=3): 5.06 (2.21); CNSI-Fe(II) 150 mg (n=3): 3.60 (0.48).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Evaluated as CR (Complete Response) in the Preliminary Efficacy Assessment. [Observation period for a single dose is 21~28 days, the observation period for two doses is doubled.]. Count Of Participants, Participants. CNSI-Fe(II) 30 mg (n=3): 0; CNSI-Fe(II) 60 mg (n=4): 0; CNSI-Fe(II) 90 mg (n=5): 0; CNSI-Fe(II) 120 mg (n=3): 0; CNSI-Fe(II) 150 mg (n=3): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Evaluated as PR (Partial Response) in the Preliminary Efficacy Assessment. [Observation period for a single dose is 21~28 days, the observation period for two doses is doubled.]. Count Of Participants, Participants. CNSI-Fe(II) 30 mg (n=3): 1; CNSI-Fe(II) 60 mg (n=4): 1; CNSI-Fe(II) 90 mg (n=5): 0; CNSI-Fe(II) 120 mg (n=3): 0; CNSI-Fe(II) 150 mg (n=3): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Evaluated as SD (Stable Disease) in the Preliminary Efficacy Assessment. [Observation period for a single dose is 21~28 days, the observation period for two doses is doubled.]. Count Of Participants, Participants. CNSI-Fe(II) 30 mg (n=3): 1; CNSI-Fe(II) 60 mg (n=4): 2; CNSI-Fe(II) 90 mg (n=5): 5; CNSI-Fe(II) 120 mg (n=3): 3; CNSI-Fe(II) 150 mg (n=3): 3.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Evaluated as PD (Progressive Disease) in the Preliminary Efficacy Assessment. [Observation period for a single dose is 21~28 days, the observation period for two doses is doubled.]. Count Of Participants, Participants. CNSI-Fe(II) 30 mg (n=3): 1; CNSI-Fe(II) 60 mg (n=4): 1; CNSI-Fe(II) 90 mg (n=5): 0; CNSI-Fe(II) 120 mg (n=3): 0; CNSI-Fe(II) 150 mg (n=3): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Cmax (ng/mL) Profile Assessment of CNSI-Fe(II) of Second Dosage [72 h post second dosage (The second dosing occurs 22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 3371.50 (296.28); CNSI-Fe(II) 90 mg (n=3): 8623.00 (8582.28).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Tmax (h) Profile Assessment of CNSI-Fe(II) of Second Dosage [72 h post second dosage (The second dosing occurs 22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, time (h) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 0.08 (0.00); CNSI-Fe(II) 90 mg (n=3): 0.14 (0.09).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: AUC (ng•h/mL) Profile Assessment of CNSI-Fe(II) of Second Dosage [72 h post second dosage (The second dosing occurs 22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, h*ng/mL (Standard Deviation). AUC (0 ~ 72 h): CNSI-Fe(II) 60 mg (n=2): 13002.57 (3458.25); CNSI-Fe(II) 90 mg (n=3): 32017.68 (34657.49). AUC (0 ~ ∞): CNSI-Fe(II) 60 mg (n=2): 14865.68 (1617.36); CNSI-Fe(II) 90 mg (n=3): 33650.19 (34384.97).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: t1/2 (h) Profile Assessment of CNSI-Fe(II) of Second Dosage [72 h post second dosage (The second dosing occurs 22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, time (h) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 3.24 (0.57); CNSI-Fe(II) 90 mg (n=3): 4.52 (2.91).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 1 h Before First Dosage [at -1 h of a time frame of 72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 0.00 (0.00); CNSI-Fe(II) 60 mg (n=4): 0.00 (0.00); CNSI-Fe(II) 90 mg (n=6): 0.00 (0.00); CNSI-Fe(II) 120 mg (n=3): 0.00 (0.00); CNSI-Fe(II) 150 mg (n=3): 0.00 (0.00).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 5 Min of First Dosage [at 5 min of a time frame of 72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 3627.00 (908.42); CNSI-Fe(II) 60 mg (n=4): 6117.00 (4136.63); CNSI-Fe(II) 90 mg (n=6): 3363.50 (3725.84); CNSI-Fe(II) 120 mg (n=3): 2081.00 (1623.52); CNSI-Fe(II) 150 mg (n=3): 3453.50 (1030.25).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 10 Min of First Dosage [at 10 min of a time frame of 72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 2462.67 (1006.52); CNSI-Fe(II) 60 mg (n=4): 4433.00 (2075.13); CNSI-Fe(II) 90 mg (n=6): 3123.83 (3345.62); CNSI-Fe(II) 120 mg (n=3): 1829.50 (791.25); CNSI-Fe(II) 150 mg (n=3): 13891.00 (17933.42).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 15 Min of First Dosage [at 15 min of a time frame of 72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 6553.00 (6514.03); CNSI-Fe(II) 60 mg (n=4): 4269.67 (1870.56); CNSI-Fe(II) 90 mg (n=6): 3076.50 (3019.85); CNSI-Fe(II) 120 mg (n=3): 8343.67 (10921.80); CNSI-Fe(II) 150 mg (n=3): 13338.33 (16864.40).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 30 Min of First Dosage [at 30 min of a time frame of 72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 4199.00 (2686.34); CNSI-Fe(II) 60 mg (n=4): 4959.25 (2928.53); CNSI-Fe(II) 90 mg (n=6): 2819.17 (2760.02); CNSI-Fe(II) 120 mg (n=3): 7144.33 (9238.01); CNSI-Fe(II) 150 mg (n=3): 11807.67 (14825.80).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 1 h of First Dosage [at 1 h of a time frame of 72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 4166.33 (3260.77); CNSI-Fe(II) 60 mg (n=4): 3968.00 (729.60); CNSI-Fe(II) 90 mg (n=6): 2432.67 (2049.81); CNSI-Fe(II) 120 mg (n=3): 6329.67 (8156.59); CNSI-Fe(II) 150 mg (n=3): 10478.00 (12978.06).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 2 h of First Dosage [at 2 h of a time frame of 72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 1949.33 (364.91); CNSI-Fe(II) 60 mg (n=4): 3076.25 (793.40); CNSI-Fe(II) 90 mg (n=6): 1900.00 (1572.04); CNSI-Fe(II) 120 mg (n=3): 4930.33 (5757.17); CNSI-Fe(II) 150 mg (n=3): 8106.33 (8652.61).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 4 h of First Dosage [at 4 h of a time frame of 72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 2416.00 (1827.83); CNSI-Fe(II) 60 mg (n=4): 2555.50 (590.25); CNSI-Fe(II) 90 mg (n=6): 1337.83 (1047.53); CNSI-Fe(II) 120 mg (n=3): 2906.00 (3068.73); CNSI-Fe(II) 150 mg (n=3): 5476.67 (5667.68).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 8 h of First Dosage [at 8 h of a time frame of 72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 292.33 (179.53); CNSI-Fe(II) 60 mg (n=4): 1324.00 (598.48); CNSI-Fe(II) 90 mg (n=6): 811.40 (999.84); CNSI-Fe(II) 120 mg (n=3): 1262.67 (1523.64); CNSI-Fe(II) 150 mg (n=3): 2613.00 (2754.00).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 12 h of First Dosage [at 12 h of a time frame of 72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 0.00 (0.00); CNSI-Fe(II) 60 mg (n=4): 677.50 (566.56); CNSI-Fe(II) 90 mg (n=6): 99.20 (133.45); CNSI-Fe(II) 120 mg (n=3): 675.67 (1170.29); CNSI-Fe(II) 150 mg (n=3): 1376.33 (1923.36).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 24 h of First Dosage [at 24 h of a time frame of 72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 0.00 (0.00); CNSI-Fe(II) 60 mg (n=4): 0.00 (0.00); CNSI-Fe(II) 90 mg (n=6): 138.33 (214.40); CNSI-Fe(II) 120 mg (n=3): 214.67 (371.81); CNSI-Fe(II) 150 mg (n=3): 47.33 (81.98).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 48 h of First Dosage [at 48 h of a time frame of 72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 0.00 (0.00); CNSI-Fe(II) 60 mg (n=4): 0.00 (0.00); CNSI-Fe(II) 90 mg (n=6): 0.00 (0.00); CNSI-Fe(II) 120 mg (n=3): 0.00 (0.00); CNSI-Fe(II) 150 mg (n=3): 0.00 (0.00).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 72 h of First Dosage [at 72 h of a time frame of 72 h]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 30 mg (n=3): 0.00 (0.00); CNSI-Fe(II) 60 mg (n=4): 0.00 (0.00); CNSI-Fe(II) 90 mg (n=6): 0.00 (0.00); CNSI-Fe(II) 120 mg (n=3): 0.00 (0.00); CNSI-Fe(II) 150 mg (n=3): 0.00 (0.00).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 1 h Before Second Dosage [1 h (of a time frame of 72 h) before second dosage (22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 0.00 (0.00); CNSI-Fe(II) 90 mg (n=3): 0.00 (0.00).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 5 Min of Second Dosage [at 5 min (of a time frame of 72 h) of second dosage (22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 3371.50 (296.28); CNSI-Fe(II) 90 mg (n=3): 8478.67 (8787.13).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 10 Min of Second Dosage [at 10 min (of a time frame of 72 h) of second dosage (22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 3060.00 (93.34); CNSI-Fe(II) 90 mg (n=3): 7695.67 (8297.76).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 15 Min of Second Dosage [at 15 min (of a time frame of 72 h) of second dosage (22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 2869.50 (91.22); CNSI-Fe(II) 90 mg (n=3): 7485.00 (7915.82).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 30 Min of Second Dosage [at 30 min (of a time frame of 72 h) of second dosage (22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 2724.00 (209.30); CNSI-Fe(II) 90 mg (n=3): 6082.33 (6471.97).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 1 h of Second Dosage [at 1 h (of a time frame of 72 h) of second dosage (22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 2140.50 (156.27); CNSI-Fe(II) 90 mg (n=3): 4873.67 (4808.39).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 2 h of Second Dosage [at 2 h (of a time frame of 72 h) of second dosage (22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 2299.00 (748.12); CNSI-Fe(II) 90 mg (n=3): 3637.67 (3637.67).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 4 h of Second Dosage [at 4 h (of a time frame of 72 h) of second dosage (22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 988.50 (314.66); CNSI-Fe(II) 90 mg (n=3): 2246.67 (2175.61).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 8 h of Second Dosage [at 8 h (of a time frame of 72 h) of second dosage (22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 579.50 (532.45); CNSI-Fe(II) 90 mg (n=3): 1637.33 (1640.51).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 12 h of Second Dosage [at 12 h (of a time frame of 72 h) of second dosage (22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 369.50 (328.80); CNSI-Fe(II) 90 mg (n=3): 674.67 (681.60).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 24 h of Second Dosage [at 24 h (of a time frame of 72 h) of second dosage (22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 0.00 (0.00); CNSI-Fe(II) 90 mg (n=3): 27.00 (46.77).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 48 h of Second Dosage [at 48 h (of a time frame of 72 h) of second dosage (22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 0.00 (0.00); CNSI-Fe(II) 90 mg (n=3): 24.33 (42.15).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Parameters Assessment: Serum Iron Concentration at 72 h of Second Dosage [at 72 h (of a time frame of 72 h) of second dosage (22~35 days after first dosing. For patient in 30 mg group, 23 days; for patients in 60 mg group, 26 and 22 days; for patients in 90 mg group, 23, 35 and 28 days; for patient in 120 mg group, 28 days.)]. Mean, concentration (ng/mL) (Standard Deviation). CNSI-Fe(II) 60 mg (n=2): 0.00 (0.00); CNSI-Fe(II) 90 mg (n=3): 13.00 (22.52).