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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Aneurysmal Subarachnoid Hemorrhage

Intervention / Treatment
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* Drug: GTX-104
* Drug: Nimodipine Capsules


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A (GTX-104 IV, Test):<br>Nimodipine was administered by infusion over 72 hours. | Drug: GTX-104<br>* new formulation of nimodipine injection for IV infusion<br>|
| Experimental: Treatment B (NIMOTOP, RLD):<br>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<br>* Nimodipine capsules (reference formulation)<br>|

What is the study measuring?
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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 |