Drug Interaction Study of ZYN002 Transdermal Gel and Probe Substrates

Harmony Biosciences Management, Inc.

Status and phase: Enrolling; Phase 1

Conditions: Drug Interaction

Treatments: Drug: Part 2; Drug: Part 1

Study type: Interventional

Funder types: Industry

Identifiers

NCT06930872

ZYN2-CL-007

Details and patient eligibility

About

This study is an open-label drug-drug interaction (DDI) study of ZYN002 transdermal gel and multiple drugs.

Full description

This study is a Phase 1, open-label, 2-part, fixed-sequence, 3-period DDI study to evaluate the effect of ZYN002 transdermal gel on the pharmacokinetics (PK) of probe substrates and their metabolites. In addition, this study is designed to evaluate the safety and tolerability of ZYN002 transdermal gel after multiple-dose topical application to healthy adult participants.

Part 1 - DDI with probe substrates for cytochrome P450 (CYP)3A4, CYP2C19, CYP2C9, CYP2D6, CYP1A2 administered as single oral doses followed by the staggered dosing of probe substrates for CYP2C8 and for CYP2B6 administered as single oral doses.

Part 2 - DDI with valproate (valproic acid [VPA]), a probe substrate for β-oxidation and glucuronidation.

Enrollment: 28 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Male or female adults, 18-55 years of age, inclusive, at the time of Screening.
2. Judged by the Investigator to be in generally good health at Screening based upon the results of a medical history, physical examination, 12-lead ECG, and clinical laboratory test results. Laboratory results outside of the reference range, but acceptable, must be documented as not clinically significant (NCS) at the discretion of the Investigator.
3. Participants must have a body mass index between 18 and 30 kg/m² at the time of Screening.
4. Females of childbearing potential must have a negative pregnancy test result at the Screening Visit and on Day -1 before admission to the CRU. Females who are not of childbearing potential are defined as being postmenopausal for >=12 months or having a history of hysterectomy and/or bilateral oophorectomy and/or bilateral tubal ligation.

Exclusion criteria

1. A) Females who are pregnant, nursing or planning to become pregnant or females of childbearing potential, who are unwilling to use medically acceptable method of contraception or B) Males with a female partner who is pregnant, nursing, or planning to become pregnant or a female partner of childbearing potential who is unwilling to use a medically acceptable method of contraception.
2. Are homozygous for CYP2C19*2 or heterozygous carriers of CYP2C19*2/CYP2C19*3 or CYP2C9*2/CYP2C9*3 or CYP2D6*2/CYP2D6*3 haplotypes categorized as poor metabolizers.
3. Has consumed alcohol 48 hours prior to Day 1 or during the study.
4. Has eaten any food or drink/beverage containing, grapefruit or grapefruit juice, apple, cranberry, Seville orange or orange juice, vegetables from the mustard family (e.g., kale, spinach, broccoli, watercress, collard greens, kohlrabi, brussels sprouts, parsley, mustard greens, endive, red cabbage, asparagus, or mustard), and chargrilled meats within one week prior to study start (Day -1).

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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28 participants in 2 patient groups

Part 1: Interaction of ZYN002 and substrates

Experimental group

Description:

Substrates: midazolam, omeprazole, losartan, dextromethorphan, caffeine, repaglinide, and bupropion

Treatment:

Drug: Part 1

Part 2: Interaction of ZYN002 and VPA

Experimental group

Treatment:

Drug: Part 2