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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Dextromethorphan HBr; Drug: GC4419

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Inventiv Health Clinical - Research Pharmacy Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.

2. Healthy as defined by:

   1. the absence of clinically significant illness and surgery within 4 weeks prior to dosing.
   2. the absence of clinically significant history of neurological, endocrinal, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
3. 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:
4. 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:
5. 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.
6. Male subjects must be willing not to donate sperm until 90 days following the last study drug administration.
7. Capable of consent.
8. Consent to perform genotyping for CYP2D6.

Exclusion Criteria:

1. Any clinically significant abnormality at physical examination, clinically significant abnormal laboratory test results
2. Positive urine drug screen or urine cotinine test at screening.
3. History of allergic reactions to GC4419, DM, or other related drugs.
4. Use of any drugs known to induce or inhibit hepatic drug metabolism within 30 days prior to the first DM administration.
5. Poor CYP2D6 metabolizers as determined by genetic testing.
6. Positive pregnancy test at screening.
7. Any reason which, in the opinion of the Principal Investigator, would prevent the subject from participating in the study.
8. Clinically significant ECG abnormalities or vital sign abnormalities
9. History of significant alcohol abuse within one year prior to screening or regular use of alcohol within six months prior to the screening visit
10. History of significant drug abuse
11. 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.
12. Use of medication other than hormonal contraceptives and topical products without significant systemic absorption:
13. Donation of plasma within 7 days prior to dosing.
14. Breast-feeding subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Galera Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2019
• Primary Completion (Actual): February 15, 2019
• Study Completion (Actual): February 15, 2019

Study Registration Dates

• First Submitted: December 21, 2018
• First Submitted That Met QC Criteria: January 2, 2019
• First Posted (Actual): January 4, 2019

Study Record Updates

• Last Update Posted (Actual): June 19, 2019
• Last Update Submitted That Met QC Criteria: June 17, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antitussive Agents; Dextromethorphan; Avasopasem manganese
• Other Study ID Numbers: GTI-4419-005

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
• product manufactured in and exported from the U.S.: No