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

A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-Praliciguat ([14C]-IW-1973) Following a Single Oral Dose in Healthy Male Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: [14C]-praliciguat

• 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: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Healthy Male Volunteers; Single oral dose of [14C]-praliciguat	Drug: [14C]-praliciguat; 10 mg praliciguat containing approximately 500 μCi of [14C]-praliciguat; Other Names: [14C]-IW-1973

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
Area under the concentration-time curve (AUC) from time zero to infinity (AUC0-inf) of praliciguat 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 praliciguat 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 praliciguat in plasma	up to Day 15
Cmax of total radioactivity in plasma and whole blood	up to Day 15
Time of Cmax (Tmax) of praliciguat 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 praliciguat in plasma	up to Day 15
t1/2 total radioactivity in plasma and whole blood	up to Day 15
Apparent total clearance of praliciguat (CL/F)	up to Day 15
Apparent volume of distribution of praliciguat (Vz/F)	up to Day 15
AUC0-inf of plasma praliciguat concentration relative to AUC0-inf of plasma total radioactivity (AUC0-inf Ratio of Plasma Praliciguat/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	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: John Hanrahan, MD, Ironwood Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2019
• Primary Completion (ACTUAL): April 24, 2019
• Study Completion (ACTUAL): April 24, 2019

Study Registration Dates

• First Submitted: January 24, 2019
• First Submitted That Met QC Criteria: January 24, 2019
• First Posted (ACTUAL): January 28, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 19, 2019
• Last Update Submitted That Met QC Criteria: June 18, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Guanylyl Cyclase C Agonists; Enzyme Activators; Praliciguat
• Other Study ID Numbers: PRL-105

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
• product manufactured in and exported from the U.S.: No