Clinical trial NCT03818295: A Trial to Study the Absorption, Metabolism, and Excretion of [14C]-Praliciguat in Healthy Male Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Cyclerion Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-01-28
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 praliciguat and total radioactivity and to assess the elimination of total radioactivity from a single oral dose of \[14C\]-praliciguat.


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 praliciguat 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 praliciguat 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 praliciguat 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 praliciguat 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 praliciguat 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 praliciguat (CL/F)
timeFrame: up to Day 15
measure: Apparent volume of distribution of praliciguat (Vz/F)
timeFrame: up to Day 15
measure: AUC0-inf of plasma praliciguat concentration relative to AUC0-inf of plasma total radioactivity (AUC0-inf Ratio of Plasma Praliciguat/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: John Hanrahan, MD
role: STUDY_DIRECTOR
References: