SUNCIST: A Study of Calmangafodipir in Healthy Japanese and Caucasian Subjects

Study Overview
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Brief Summary
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Randomized, double-bline, placebo-controlled, single dose study comparing the pharmacokinetics (PK) and safety of PP095-01 in Japanese and non-Asian (eg, Caucasian) subjects.

Official Title
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SUNCIST: A Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending, Single-Dose Study to Assess the Safety, Tolerability, Pharmacokinetics of Intravenous Administration of Calmangafodipir in Healthy Japanese and Caucasian Subjects

Conditions
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Chemotherapy Induced Peripheral Neuropathy (CIPN)

Intervention / Treatment
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* Drug: Calmangafodipir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI within 18.0 to 30.0 kg/m2 and body weight not less than 50 kg Blood pressure between 90 and 140 mmHg systolic, and no higher than 90 mmHg diastolic Non-smoker or not smoking for at least 12 months Be first generation Japanese (For Group 1 only), defined as: Born in Japan Has 2 Japanese biological parents and 4 Japanese biological grandparents Has lived outside of Japan for less than 5 years Has made no significant changes in lifestyle, including diet, since leaving Japan Exclusion Criteria: Clinically significant abnormal values for hematology, clinical chemistry, urinalysis, physical exam, vital signs, or electrocardiogram at screening Has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV; has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening. Has a history of drug or alcohol abuse Has previously received calmangafodipir or mangafodipir Welders, mine workers, or other workers in occupations (current or past) where high manganese exposure is likely

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 (Japanese) Calmangafodipir<br> | Drug: Calmangafodipir<br>* Single ascending doses of 2 μmol/kg, 5 μmol/kg, and 10 μmol/kg<br>|
| Placebo Comparator: Group 1 (Japanese) Placebo<br> | Drug: Placebo<br>* Placebo<br>|
| Experimental: Group 2 (Caucasian) Calmangafodipir<br> | Drug: Calmangafodipir<br>* Single ascending doses of 2 μmol/kg, 5 μmol/kg, and 10 μmol/kg<br>|
| Placebo Comparator: Group 2 (Caucasian) Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment-emergent adverse events | Subject incidence of treatment-emergent adverse events (TEAEs), which may include changes in laboratory safety tests, electrocardiograms (ECG), and vital signs. | From signing of informed consent through the last follow up visit (up to Day 10) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum plasma concentration during a dosing interval | predose and 1 min, 15 min, 30 min, 1 hour, 4 hours, and 8 hours postdose | 
| tmax | Time to reach maximum plasma concentration | predose and 1 min, 15 min, 30 min, 1 hour, 4 hours, and 8 hours postdose | 
| AUC(0-last) | Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration | predose and 1 min, 15 min, 30 min, 1 hour, 4 hours, and 8 hours postdose | 
| Ae | Amount of manganese and zinc excreted into urine | 4 hours post-dose and 24 hours post-dose | 
| Ae% | Percent of study drug manganese excreted into urine | 4 hours and 24 hours post-dose |