A Trial to Study the Absorption, Metabolism, and Excretion of [14C]-Olinciguat in Healthy Male Volunteers

Study Overview
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Brief Summary
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The primary objective is to characterize the pharmacokinetics (PK) of olinciguat and total radioactivity and to assess the elimination of total radioactivity from a single oral dose of [14C]-olinciguat.

Detailed Description
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OLI-103 is a Phase 1 open-label, nonrandomized, single-dose study in up to 8 subjects that will be conducted at a single center in the US. Safety assessments will be performed throughout the clinic period and multiple PK samples will be collected. Subjects will be confined to the clinical research center for at least 8 days. The purpose of the study is to determine the absorption, metabolism, and excretion of [14C]-olinciguat and to characterize and determine, where possible, the metabolites present in plasma, urine, and feces after a single oral dose. The study will help identify and characterize olinciguat metabolites, evaluate the likelihood of effects of liver or kidney impairment on the disposition of olinciguat, and assess the likelihood of drug-drug interactions with olinciguat.

Official Title
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A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-Olinciguat ([14C]-IW-1701) Following a Single Oral Dose in Healthy Male Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: [14C]-olinciguat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males of any race, between 18 and 55 years of age, inclusive Body mass index between 18 and 32 kg/m2, inclusive Subject is in good health and has no clinically significant findings on physical examination Men must agree to use protocol-specified contraception and also to not donate sperm throughout the study and for at least 90 days after the final dose of study drug Exclusion Criteria: Any active or unstable clinically significant medical condition Use of any prescribed or non-prescribed medication Additional inclusion/exclusion criteria may apply per protocol

Ages Eligible for Study
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Minimum Age: 18 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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Male Volunteers<br>Single oral dose of [14C]-olinciguat | Drug: [14C]-olinciguat<br>* oral capsule<br>* Other names: 14C-IW-1701;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of total radioactivity excreted in urine (Aeu) and feces (Aef) |  | up to Day 15 | 
| Cumulative Aeu and cumulative Aef |  | up to Day 15 | 
| Percentage of total radioactivity excreted in urine (feu) and feces (fef) |  | up to Day 15 | 
| Cumulative feu and cumulative fef |  | up to Day 15 | 
| Percentage of total radioactivity in total excreta (feces + urine) |  | up to Day 15 | 
| Area under the concentration-time curve (AUC) from time zero to infinity (AUC0-inf) of olinciguat in plasma |  | up to Day 15 | 
| AUC0-inf of total radioactivity in plasma and whole blood |  | up to Day 15 | 
| AUC from time zero to the last quantifiable concentration (AUC0-last) of olinciguat in plasma |  | up to Day 15 | 
| AUC0-last of total radioactivity in plasma and whole blood |  | up to Day 15 | 
| Maximum observed concentration (Cmax) of olinciguat in plasma |  | up to Day 15 | 
| Cmax of total radioactivity in plasma and whole blood |  | up to Day 15 | 
| Time of Cmax (Tmax) of olinciguat in plasma |  | up to Day 15 | 
| Tmax of total radioactivity in plasma and whole blood |  | up to Day 15 | 
| Apparent terminal elimination half-life (t1/2) of olinciguat in plasma |  | up to Day 15 | 
| t1/2 total radioactivity in plasma and whole blood |  | up to Day 15 | 
| Apparent total clearance of olinciguat (CL/F) |  | up to Day 15 | 
| Apparent volume of distribution of olinciguat (Vz/F) |  | up to Day 15 | 
| AUC0-inf of plasma olinciguat concentration relative to AUC0-inf of plasma total radioactivity (AUC0-inf Ratio of Plasma Olinciguat/Plasma Total Radioactivity) |  | up to Day 15 | 
| AUC0-inf of whole blood total radioactivity to AUC0-inf of plasma total radioactivity (AUC0-inf Ratio of Blood Total Radioactivity/Plasma Total Radioactivity) |  | up to Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of metabolite radioactivity excreted in urine and feces |  | up to Day 15 | 
| AUC0-inf of metabolite radioactivity levels in plasma |  | up to Day 15 | 
| AUC0-inf of plasma metabolite radioactivity levels relative to AUC0-inf of plasma total radioactivity (Plasma AUC0-inf Ratio of Metabolite Radioactivity/Total Radioactivity) |  | up to Day 15 | 
| Chromatographic retention time of metabolites |  | up to Day 15 | 
| Molecular ion mass of metabolites |  | up to Day 15 | 
| Characteristic mass spectrometry fragmentation ions of metabolites |  | up to Day 15 | 
| Chemical structures (graphical representations showing atom connectivity) proposed for plasma, urine, and feces metabolites |  | up to Day 15 | 
| Number(s) of participants with ≥1 treatment-emergent serious adverse event (SAE) |  | up to Day 15 | 
| Number(s) of participants with ≥1 adverse event (AE) leading to study drug discontinuation |  | up to Day 15 | 
| Number(s) of participants with ≥1 Grade ≥3 AE (per CTCAE v. 5.0) |  | up to Day 15 | 
| Number(s) of participants with ≥1 clinically significant abnormal physical examination finding |  | up to Day 15 |