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

Phase 1
Completed
Conditions
Healthy Volunteers
Interventions
Drug: [14C]-olinciguat
Registration Number
NCT03795519
Lead Sponsor
Cyclerion Therapeutics
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
8
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Healthy Male Volunteers[14C]-olinciguatSingle oral dose of \[14C\]-olinciguat
Primary Outcome Measures
NameTimeMethod
Cumulative feu and cumulative fefup to Day 15
Cmax of total radioactivity in plasma and whole bloodup to Day 15
Tmax of total radioactivity in plasma and whole bloodup to Day 15
Apparent volume of distribution of olinciguat (Vz/F)up to Day 15
Amount of total radioactivity excreted in urine (Aeu) and feces (Aef)up to Day 15
Cumulative Aeu and cumulative Aefup to Day 15
Percentage of total radioactivity excreted in urine (feu) and feces (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 plasmaup to Day 15
AUC0-inf of total radioactivity in plasma and whole bloodup to Day 15
AUC from time zero to the last quantifiable concentration (AUC0-last) of olinciguat in plasmaup to Day 15
AUC0-last of total radioactivity in plasma and whole bloodup to Day 15
Maximum observed concentration (Cmax) of olinciguat in plasmaup to Day 15
Time of Cmax (Tmax) of olinciguat in plasmaup to Day 15
Apparent total clearance of olinciguat (CL/F)up to Day 15
Apparent terminal elimination half-life (t1/2) of olinciguat in plasmaup to Day 15
t1/2 total radioactivity in plasma and whole bloodup 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
NameTimeMethod
AUC0-inf of metabolite radioactivity levels in plasmaup to Day 15
Molecular ion mass of metabolitesup to Day 15
Levels of metabolite radioactivity excreted in urine and fecesup 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 metabolitesup to Day 15
Characteristic mass spectrometry fragmentation ions of metabolitesup to Day 15
Chemical structures (graphical representations showing atom connectivity) proposed for plasma, urine, and feces metabolitesup 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 clinically significant abnormal physical examination findingup to Day 15
Number(s) of participants with ≥1 adverse event (AE) leading to study drug discontinuationup to Day 15
Number(s) of participants with ≥1 Grade ≥3 AE (per CTCAE v. 5.0)up to Day 15

Trial Locations

Locations (1)

Covance Clinical Research Unit Inc.

🇺🇸

Madison, Wisconsin, United States

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