Pharmacokinetics and Excretion of Oral [14C]-Rodatristat Ethyl

NCT05006118 | Completed Phase 1 FDA Drug

• 1 other identifier: RVT-1201-1003
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label study to evaluate the PK and excretion of a single oral dose of \[14C\]-rodatristat ethyl. The study will consist of: Screening evaluations (within 29 days prior to dosing); a treatment phase (from dosing until discharge from the unit, a minimum of 7 days and a maximum of 14 days); and discharge procedures.

Conditions

Healthy

Keywords

Pulmonary Arterial Hypertension; PAH

Outcome Measures

Primary Outcomes (1)

• Overall, urinary, and fecal recovery of total radioactivity as a percentage of administered dose.

  15 days or until total recovery (urine and feces combined) of the administered radioactive dose is ≥90% and the total daily recovery of radioactive dose is ≤1% on 2 consecutive days in which a fecal sample is collected

Secondary Outcomes (14)

• Plasma AUC(0-t) of total radioactivity, rodatristat ethyl, rodatristat, M15, and other metabolites if appropriate.

  15 days or until total recovery (urine and feces combined) of the administered radioactive dose is ≥90% and the total daily recovery of radioactive dose is ≤1% on 2 consecutive days in which a fecal sample is collected

• Plasma AUC(0-∞) of total radioactivity, rodatristat ethyl, rodatristat, M15, and other metabolites if appropriate.

  15 days or until total recovery (urine and feces combined) of the administered radioactive dose is ≥90% and the total daily recovery of radioactive dose is ≤1% on 2 consecutive days in which a fecal sample is collected

• Plasma Cmax of total radioactivity, rodatristat ethyl, rodatristat, M15, and other metabolites if appropriate.

  15 days or until total recovery (urine and feces combined) of the administered radioactive dose is ≥90% and the total daily recovery of radioactive dose is ≤1% on 2 consecutive days in which a fecal sample is collected

• Plasma tmax of total radioactivity, rodatristat ethyl, rodatristat, M15, and other metabolites if appropriate.

  15 days or until total recovery (urine and feces combined) of the administered radioactive dose is ≥90% and the total daily recovery of radioactive dose is ≤1% on 2 consecutive days in which a fecal sample is collected

• Plasma CL/F of total radioactivity, rodatristat ethyl, rodatristat, M15, and other metabolites if appropriate.

  15 days or until total recovery (urine and feces combined) of the administered radioactive dose is ≥90% and the total daily recovery of radioactive dose is ≤1% on 2 consecutive days in which a fecal sample is collected

Study Arms (1)

Radio-labeled rodatristat ethyl 600 mg

EXPERIMENTAL

Single dose of rodatristat ethyl 600 mg as an oral suspension containing a mixture of \[12C\]-rodatristat ethyl and \[14C\]-rodatristat ethyl to contain approximately 600 microcuries (uCi) of radioactivity

Drug: Radio-labeled rodatristat ethyl 600 mg

Interventions

Radio-labeled rodatristat ethyl 600 mg DRUG

Single dose of rodatristat ethyl 600 mg as an oral suspension containing a mixture of \[12C\]-rodatristat ethyl and \[14C\]-rodatristat ethyl to contain approximately 600 microcuries (uCi) of radioactivity

Radio-labeled rodatristat ethyl 600 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males aged 18 to 55 years, inclusive.
• Healthy subjects are defined as individuals free from clinically significant illness or disease as determined by their medical history, physical examination, vital signs, cardiac monitoring, and clinical laboratory test results.
• Male subjects must agree to use contraception as detailed in Section 5.4.1 starting at Screening, during the treatment period, and for at least 100 days after the last dose of investigational product (IP), and refrain from donating sperm during this period.
• Body mass index (BMI) ≥ 18 kg/m2 and ≤ 32 kg/m2
• Capable of giving signed informed consent, able to understand and comply with protocol requirements, instructions, and protocol-related restrictions, and likely to complete the study as planned.
• History of regular bowel movements (averaging one or more bowel movements per day).

You may not qualify if:

• Any known preexisting medical or psychiatric condition that could interfere with the subject's ability to provide informed consent or participate in study conduct, or that may confound study findings including, but not limited to a history of clinically significant gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, neurological, psychiatric, or cardiovascular disease
• History of Gilbert's Syndrome
• History of any allergy that, in the opinion of the Investigator, contraindicates participation in the trial.
• Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at Screening) of 50 mL to 499 mL of blood within 30 days or more than 499 mL within 56 days prior to Day 1.
• Participation in an investigational drug, vaccine, or device study, where last administration of the investigational drug (new chemical entity) is within 30 days or 5 half-lives whichever is longer before IP administration or 90 days for a biologic study.
• Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy (e.g., cholecystectomy) or motility, or with abnormal hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the IP (appendectomy and hernia repair would be acceptable).
• Subjects who have participated in more than 3 radiolabeled drug studies in the last 12 months (previous study to be at least 4 months prior to check-in to the study site where exposures are known to the Investigator or 6 months prior to check-in to the study site for a radiolabeled drug study where exposures are not known to the Investigator).
• Clinically significant ECG abnormalities (i.e., QTcF \> 450 msec) prior to dosing (Screening and Day -1) that are confirmed by a repeat reading.
• Abnormal blood pressure, either low (defined as \< 90 mmHg systolic and/or \< 50 mmHg diastolic) or high (defined as \> 140 mmHg systolic and/or \> 90 mmHg diastolic) at Screening or Day -1 that is confirmed by a repeat reading.
• Clinically significant abnormalities in laboratory test results (hematology, coagulation, chemistry panel, and urinalysis) at Screening or Day -1 that are confirmed by a repeat reading
• Creatinine clearance \< 80 mL/min at Screening or Day -1, calculated using the Cockcroft-Gault formula.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values greater than upper limit of normal (ULN) at Screening or Day -1. A single repeat measurement is allowed for eligibility determination.
• Positive urine test for drugs of abuse (including cotinine) at Screening or Day 1.
• Positive alcohol test (breath, saliva, or urine) at Day 1.
• Use of prescription or nonprescription drugs, including high dose vitamins, dietary supplements (including St. John's Wort) within 7 days or 5 halflives of the prescription or nonprescription drug (whichever was longer) prior to the first dose of IP, unless in the opinion of the Investigator and Sponsor, the medication would not interfere with the study outcomes or compromise subject safety.

Sponsors & Collaborators

• Altavant Sciences GmbH: lead
• Altavant Sciences, Inc.: collaborator
• Covance: collaborator

Study Sites (1)

Covance Clinical Research Unit

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• John E Blanchard, MD

  Covance Clinical Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2021
• First Posted: August 16, 2021
• Study Start: September 23, 2021
• Primary Completion: October 6, 2021
• Study Completion: October 6, 2021
• Last Updated: July 13, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)