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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: [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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance Clinical Research Unit Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Male Volunteers; Single oral dose of [14C]-olinciguat	Drug: [14C]-olinciguat; oral capsule; Other Names: 14C-IW-1701

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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
AUC0-inf of total radioactivity in plasma and whole blood	up to Day 15
AUC0-last of total radioactivity in plasma and whole blood	up to Day 15
Cmax of total radioactivity in plasma and whole blood	up to Day 15
Tmax of total radioactivity in plasma and whole blood	up to Day 15
t1/2 total radioactivity in plasma and whole blood	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
Area under the concentration-time curve (AUC) from time zero to infinity (AUC0-inf) of olinciguat in plasma	up to Day 15
AUC from time zero to the last quantifiable concentration (AUC0-last) of olinciguat in plasma	up to Day 15
Maximum observed concentration (Cmax) of olinciguat in plasma	up to Day 15
Time of Cmax (Tmax) of olinciguat in plasma	up to Day 15
Apparent terminal elimination half-life (t1/2) of olinciguat in plasma	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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Cyclerion Therapeutics
• Investigators: Study Director: Bina Tejura, MD, Ironwood Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2019
• Primary Completion (Actual): February 27, 2019
• Study Completion (Actual): February 27, 2019

Study Registration Dates

• First Submitted: December 14, 2018
• First Submitted That Met QC Criteria: January 3, 2019
• First Posted (Actual): January 7, 2019

Study Record Updates

• Last Update Posted (Actual): April 3, 2019
• Last Update Submitted That Met QC Criteria: April 1, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: OLI-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No