Relative Bioavailability of Intravenous GTX-104 Compared to Oral Nimodipine Capsules in Healthy Subjects

A Phase 1, Randomized, Two-Period Crossover Study to Evaluate the Relative Bioavailability of Intravenous GTX-104 Compared to Oral Nimodipine Capsules at Steady State in Healthy Male and Female Subjects

This is a Phase 1, single center, randomized, two-period crossover study in healthy male and female subjects designed to evaluate the relative bioavailability (BA) and safety at steady state of two formulations of nimodipine: GTX 104 (nimodipine for intravenous [IV] infusion; test formulation) and nimodipine oral capsules, RS (reference formulation).

Study Overview

• Status: Completed
• Conditions: Aneurysmal Subarachnoid Hemorrhage
• Intervention / Treatment: Drug: GTX-104; Drug: Nimodipine Capsules

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Montréal, Canada
    • Clinical Research Unit

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subject had a body mass index between 18 and 32 kg/m2, inclusive.
• Subject was in good general physical health as determined by absence of clinically significant (CS) medical or psychiatric history, physical examination findings, vital signs, clinical laboratory evaluations, and 12-lead ECG measurements.

Exclusion Criteria:

• History or presence of clinically significant medical illness, including, but not limited to, cardiovascular, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic, psychiatric, renal, hepatic, chronic respiratory, or gastrointestinal disease, that could have interfered with the interpretation of the study.
• Had current or recent (within 6 months) history of gastrointestinal disease or any surgical or medical condition (eg, Crohn's or liver disease) that could potentially alter the absorption, metabolism, or excretion of the study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A (GTX-104 IV, Test): Nimodipine was administered by infusion over 72 hours.	Drug: GTX-104; new formulation of nimodipine injection for IV infusion
Experimental: Treatment B (NIMOTOP, RLD): Nimodipine capsules (RS) administered orally with 240 mL of water at a dose level of 60 mg (two 30 mg capsules) q4h for 72 hours.	Drug: Nimodipine Capsules; Nimodipine capsules (reference formulation)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax Day 1	Maximum concentration	Day 1 for the first dose (8:00 AM dose)
AUC (AUCDay 3, 0-24hr)	Area under the concentration-time curve	Day 3 from 8:00 AM to 8:00 AM from 0 to 24 hr

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax Day 3 across all 6 doses	Maximum concentration across all doses	Day 3
Absolute bioavailability (F) Day 3	the ratio of geometric LSmeans with corresponding 90% confidence interval calculated from the exponential of the difference between the Treatment-1 and Treatment-2 for the ln-transformed parameters Cmax Day3	Day 3
Total body clearance of the drug from plasma after IV infusion (CL) Day 3	(Dosedaily/AUCDay3,0-24)	Day 3 from 8:00 AM to 8:00 AM from 0 to 24 h
Apparent total body clearance of the drug from plasma after oral administration (CL/F) Day 3	Dosedaily/AUCDay 3 0-24	Day 3 from 8:00 AM to 8:00 AM from 0 to 24 h

Collaborators and Investigators

• Sponsor: Acasti Pharma Inc.
• Investigators: Principal Investigator: Eric Sicard, MD, Clinical Research Unit

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2021
• Primary Completion (Actual): February 17, 2022
• Study Completion (Actual): February 24, 2022

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: June 10, 2022
• First Posted (Actual): June 14, 2022

Study Record Updates

• Last Update Posted (Estimated): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Nimodipine
• Other Study ID Numbers: GTX-104-002

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