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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03795519
• Other study ID #: OLI-103
• Status: Completed
• Phase: Phase 1
• Start date: January 17, 2019
• Est. completion date: February 27, 2019

Study information

• Verified date: April 2019
• Source: Cyclerion Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: February 27, 2019
• Est. primary completion date: February 27, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• [14C]-olinciguat
oral capsule

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit Inc.	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Cyclerion Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Amount of total radioactivity excreted in urine (Aeu) and feces (Aef)		up to Day 15
Primary	Cumulative Aeu and cumulative Aef		up to Day 15
Primary	Percentage of total radioactivity excreted in urine (feu) and feces (fef)		up to Day 15
Primary	Cumulative feu and cumulative fef		up to Day 15
Primary	Percentage of total radioactivity in total excreta (feces + urine)		up to Day 15
Primary	Area under the concentration-time curve (AUC) from time zero to infinity (AUC0-inf) of olinciguat in plasma		up to Day 15
Primary	AUC0-inf of total radioactivity in plasma and whole blood		up to Day 15
Primary	AUC from time zero to the last quantifiable concentration (AUC0-last) of olinciguat in plasma		up to Day 15
Primary	AUC0-last of total radioactivity in plasma and whole blood		up to Day 15
Primary	Maximum observed concentration (Cmax) of olinciguat in plasma		up to Day 15
Primary	Cmax of total radioactivity in plasma and whole blood		up to Day 15
Primary	Time of Cmax (Tmax) of olinciguat in plasma		up to Day 15
Primary	Tmax of total radioactivity in plasma and whole blood		up to Day 15
Primary	Apparent terminal elimination half-life (t1/2) of olinciguat in plasma		up to Day 15
Primary	t1/2 total radioactivity in plasma and whole blood		up to Day 15
Primary	Apparent total clearance of olinciguat (CL/F)		up to Day 15
Primary	Apparent volume of distribution of olinciguat (Vz/F)		up to Day 15
Primary	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
Primary	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	Levels of metabolite radioactivity excreted in urine and feces		up to Day 15
Secondary	AUC0-inf of metabolite radioactivity levels in plasma		up to Day 15
Secondary	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
Secondary	Chromatographic retention time of metabolites		up to Day 15
Secondary	Molecular ion mass of metabolites		up to Day 15
Secondary	Characteristic mass spectrometry fragmentation ions of metabolites		up to Day 15
Secondary	Chemical structures (graphical representations showing atom connectivity) proposed for plasma, urine, and feces metabolites		up to Day 15
Secondary	Number(s) of participants with =1 treatment-emergent serious adverse event (SAE)		up to Day 15
Secondary	Number(s) of participants with =1 adverse event (AE) leading to study drug discontinuation		up to Day 15
Secondary	Number(s) of participants with =1 Grade =3 AE (per CTCAE v. 5.0)		up to Day 15
Secondary	Number(s) of participants with =1 clinically significant abnormal physical examination finding		up to Day 15