Clinical trial NCT03795519: A Trial to Study the Absorption, Metabolism, and Excretion of [14C]-Olinciguat in Healthy Male Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Cyclerion Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-01-07
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Amount of total radioactivity excreted in urine (Aeu) and feces (Aef)
timeFrame: up to Day 15
measure: Cumulative Aeu and cumulative Aef
timeFrame: up to Day 15
measure: Percentage of total radioactivity excreted in urine (feu) and feces (fef)
timeFrame: up to Day 15
measure: Cumulative feu and cumulative fef
timeFrame: up to Day 15
measure: Percentage of total radioactivity in total excreta (feces + urine)
timeFrame: up to Day 15
measure: Area under the concentration-time curve (AUC) from time zero to infinity (AUC0-inf) of olinciguat in plasma
timeFrame: up to Day 15
measure: AUC0-inf of total radioactivity in plasma and whole blood
timeFrame: up to Day 15
measure: AUC from time zero to the last quantifiable concentration (AUC0-last) of olinciguat in plasma
timeFrame: up to Day 15
measure: AUC0-last of total radioactivity in plasma and whole blood
timeFrame: up to Day 15
measure: Maximum observed concentration (Cmax) of olinciguat in plasma
timeFrame: up to Day 15
measure: Cmax of total radioactivity in plasma and whole blood
timeFrame: up to Day 15
measure: Time of Cmax (Tmax) of olinciguat in plasma
timeFrame: up to Day 15
measure: Tmax of total radioactivity in plasma and whole blood
timeFrame: up to Day 15
measure: Apparent terminal elimination half-life (t1/2) of olinciguat in plasma
timeFrame: up to Day 15
measure: t1/2 total radioactivity in plasma and whole blood
timeFrame: up to Day 15
measure: Apparent total clearance of olinciguat (CL/F)
timeFrame: up to Day 15
measure: Apparent volume of distribution of olinciguat (Vz/F)
timeFrame: up to Day 15
measure: AUC0-inf of plasma olinciguat concentration relative to AUC0-inf of plasma total radioactivity (AUC0-inf Ratio of Plasma Olinciguat/Plasma Total Radioactivity)
timeFrame: up to Day 15
measure: AUC0-inf of whole blood total radioactivity to AUC0-inf of plasma total radioactivity (AUC0-inf Ratio of Blood Total Radioactivity/Plasma Total Radioactivity)
timeFrame: up to Day 15
Secondary outcomes:
measure: Levels of metabolite radioactivity excreted in urine and feces
timeFrame: up to Day 15
measure: AUC0-inf of metabolite radioactivity levels in plasma
timeFrame: up to Day 15
measure: AUC0-inf of plasma metabolite radioactivity levels relative to AUC0-inf of plasma total radioactivity (Plasma AUC0-inf Ratio of Metabolite Radioactivity/Total Radioactivity)
timeFrame: up to Day 15
measure: Chromatographic retention time of metabolites
timeFrame: up to Day 15
measure: Molecular ion mass of metabolites
timeFrame: up to Day 15
measure: Characteristic mass spectrometry fragmentation ions of metabolites
timeFrame: up to Day 15
measure: Chemical structures (graphical representations showing atom connectivity) proposed for plasma, urine, and feces metabolites
timeFrame: up to Day 15
measure: Number(s) of participants with ≥1 treatment-emergent serious adverse event (SAE)
timeFrame: up to Day 15
measure: Number(s) of participants with ≥1 adverse event (AE) leading to study drug discontinuation
timeFrame: up to Day 15
measure: Number(s) of participants with ≥1 Grade ≥3 AE (per CTCAE v. 5.0)
timeFrame: up to Day 15
measure: Number(s) of participants with ≥1 clinically significant abnormal physical examination finding
timeFrame: up to Day 15
Other outcomes:
Locations:
city: Madison
country: United States
facility: Covance Clinical Research Unit Inc.
state: Wisconsin
Study officials:
affiliation: Ironwood Pharmaceuticals, Inc.
name: Bina Tejura, MD
role: STUDY_DIRECTOR
References: