Clinical trial NCT06930872: Drug Interaction Study of ZYN002 Transdermal Gel and Probe Substrates
Official title: A Phase 1, Open Label, Drug Interaction Study to Evaluate the Effect of ZYN002 on the Pharmacokinetics of CYP3A4, CYP2C19, CYP2C9, CYP2D6, CYP1A2, CYP2C8, and CYP2B6 Probe Substrates, and Valproate in Healthy Adult Participants
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Drug Interaction
Lead sponsor: Harmony Biosciences Management, Inc.
Sponsor class: INDUSTRY
First posted: 2025-04-16
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1: Participants will receive probe substrates in Periods 1 and 3 and ZYN002 treatment in Periods 2 and 3.

Part 2: Participants will receive probe substrate in Periods 1 and 3 and ZYN002 treatment in Periods 2 and 3.
Primary purpose: OTHER

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

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Maximum measure plasma concentration (Cmax) of probe substrates and metabolites
timeFrame: Days 1-3 (Period 1), Days 24-26 (Period 3)
measure: Cmax of repaglinide and metabolite
timeFrame: Days 3 and 4 (Period 1), Days 26 and 27 (Period 3)
measure: Cmax of bupropion and metabolite
timeFrame: Days 4-10 (Period 1), Days 27-33 (Period 3)
measure: Cmax of CBD, delta-9-tetrahydrocannabinol (THC), and CBD metabolites
timeFrame: Days 24-33 (Period 3)
measure: Amount excreted in urine over the collection period (Ae0-12) of CBD and its metabolites
timeFrame: Day 17 (Period 2), Days 24 and 32 (Period 3)
measure: Cmax of VPA and metabolite
timeFrame: Days 1-4 (Period 1), Days 18-21 (Period 3)
measure: Cmax of CBD, THC, and CBD metabolites
timeFrame: Days 18-21 (Period 3)
measure: Ae0-12 of VPA and metabolites
timeFrame: Days 1-4 (Period 1), Day 17 (Period 2), Days 18-20 (Period 3)
measure: Ae0-12 of ZYN002 and metabolites
timeFrame: Day 17 (Period 2), Days 18 and 20 (Period 3)
Secondary outcomes:
measure: Number of participants with skin irritation in ZYN002 application areas
timeFrame: Up to 33 days
measure: Number of participants with abnormal physical examination results
timeFrame: Up to 33 days
measure: Number of participants with abnormal clinical laboratory results
timeFrame: Up to 33 days
measure: Number of participants with abnormal vital sign results
timeFrame: Up to 33 days
measure: Number of participants with abnormal continuous pulse oximetry results
timeFrame: Up to 33 days
measure: Number of participants with abnormal electrocardiogram (ECG)
timeFrame: Up to 33 days
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: CMAX Clinical Research
state: South Australia
Study officials:
affiliation: CMAX Clinical Research
name: Thomas Polasek, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Harmony Biosciences Management, Inc.
name: Kristen Bzdek, MD
role: STUDY_DIRECTOR
References: