Study to Evaluate the Effects of 90 mg Intravenous Infusions of GC4419 on the Single Dose Pharmacokinetics of Dextromethorphan in Healthy Adult Subjects

Study Overview
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Brief Summary
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This will be a single center, phase 1, open-label, fixed-sequence study under fasting conditions to evaluate the effect of 90 mg intravenous (IV) infusions of GC4419 on the single-dose pharmacokinetic (PK) of dextromethorphan (DM) capsules liquid filled.

Official Title
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Phase 1, Open-label, One-arm, Fixed-sequence Study to Evaluate the Effects of 90 mg Intravenous Infusions of GC4419 on the Single Dose Pharmacokinetics of Dextromethorphan in Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dextromethorphan HBr
* Drug: GC4419


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, non-smoker, ≥ 18 and ≤ 55 years of age, with BMI > 18.5 and < 30.0 kg/m2 and body weight ≥ 50.0 kg for males and ≥ 45.0 kg for females. Healthy as defined by: the absence of clinically significant illness and surgery within 4 weeks prior to dosing. the absence of clinically significant history of neurological, endocrinal, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease. Females of childbearing potential must be willing to use acceptable contraceptive method throughout the study and for 30 days after the last study drug administration: Male subjects must be willing to use acceptable contraceptive method from the first dosing until at least 90 days after the last study drug administration: Male subjects (including men who have had vasectomies) with a pregnant partner must agree to use a condom from the first dosing until at least 90 days after the last study drug administration. Male subjects must be willing not to donate sperm until 90 days following the last study drug administration. Capable of consent. Consent to perform genotyping for CYP2D6. Exclusion Criteria: Any clinically significant abnormality at physical examination, clinically significant abnormal laboratory test results Positive urine drug screen or urine cotinine test at screening. History of allergic reactions to GC4419, DM, or other related drugs. Use of any drugs known to induce or inhibit hepatic drug metabolism within 30 days prior to the first DM administration. Poor CYP2D6 metabolizers as determined by genetic testing. Positive pregnancy test at screening. Any reason which, in the opinion of the Principal Investigator, would prevent the subject from participating in the study. Clinically significant ECG abnormalities or vital sign abnormalities History of significant alcohol abuse within one year prior to screening or regular use of alcohol within six months prior to the screening visit History of significant drug abuse Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration. Use of medication other than hormonal contraceptives and topical products without significant systemic absorption: Donation of plasma within 7 days prior to dosing. Breast-feeding subject.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fixed Sequence<br> | Drug: Dextromethorphan HBr<br>* A single 60 mg dose of DM capsules liquid-filled on Day 1 and Day 3<br>Drug: GC4419<br>* Daily 90 mg IV infusions over 60 minutes on Day 3 and Day 4<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) profile for dextromethorphan (DM) (in plasma): AUC0-t |  | Pre-dose on Day 1, and at 0.5, 1 (immediately prior to the end of GC4419 infusion), 2, 3, 4, 6, 8, 12, and 24 hours after the start of infusion | 
| Pharmacokinetic (PK) profile for dextromethorphan (DM) (in plasma): AUC0-inf |  | Pre-dose on Day 1, and at 0.5, 1 (immediately prior to the end of GC4419 infusion), 2, 3, 4, 6, 8, 12, and 24 hours after the start of infusion | 
| Pharmacokinetic (PK) profile for dextromethorphan (DM) (in plasma): Cmax |  | Pre-dose on Day 1, and at 0.5, 1 (immediately prior to the end of GC4419 infusion), 2, 3, 4, 6, 8, 12, and 24 hours after the start of infusion |