Drug Interaction Study of ZYN002 Transdermal Gel and Probe Substrates
This study is an open-label drug-drug interaction (DDI) study of ZYN002 transdermal gel and multiple drugs.
Study details:
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
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Male or female adults, 18-55 years of age, inclusive, at the time of Screening.
- 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.
- Participants must have a body mass index between 18 and 30 kg/m² at the time of Screening.
- 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
- 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.
- 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.
- Has consumed alcohol 48 hours prior to Day 1 or during the study.
- 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).
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
OTHER
Phase
- PHASE1
Study ID
NCT06930872
Intervention or treatment
DRUG: Part 1
DRUG: Part 2
Conditions
- Drug Interaction
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
CMAX Clinical Research
Select from list below to view details:
CMAX Clinical Research
Adelaide, South Australia, Australia
Loading map...
Who is running the clinical trial?
Harmony Biosciences Management, Inc.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Part 1: Interaction of ZYN002 and substrates
| Drug: Part 1 |
EXPERIMENTAL: Part 2: Interaction of ZYN002 and VPA
| Drug: Part 2 |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Maximum measure plasma concentration (Cmax) of probe substrates and metabolites | Blood samples collected at pre dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose. | Days 1-3 (Period 1), Days 24-26 (Period 3) |
| Cmax of repaglinide and metabolite | Blood samples collected at pre dose, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose. | Days 3 and 4 (Period 1), Days 26 and 27 (Period 3) |
| Cmax of bupropion and metabolite | Blood samples collected at pre dose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 48, 72, 96, 120, and 144 hours post dose. | Days 4-10 (Period 1), Days 27-33 (Period 3) |
| Cmax of CBD, delta-9-tetrahydrocannabinol (THC), and CBD metabolites | Blood samples collected at pre dose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose. | Days 24-33 (Period 3) |
| Amount excreted in urine over the collection period (Ae0-12) of CBD and its metabolites | Urine samples collected over a 12-hour period. | Day 17 (Period 2), Days 24 and 32 (Period 3) |
| Cmax of VPA and metabolite | Blood samples collected at pre dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post dose. | Days 1-4 (Period 1), Days 18-21 (Period 3) |
| Cmax of CBD, THC, and CBD metabolites | Blood samples collected at pre dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post dose. | Days 18-21 (Period 3) |
| Ae0-12 of VPA and metabolites | Urine samples collected over a 12-hour period. | Days 1-4 (Period 1), Day 17 (Period 2), Days 18-20 (Period 3) |
| Ae0-12 of ZYN002 and metabolites | Urine samples collected over a 12-hour period. | Day 17 (Period 2), Days 18 and 20 (Period 3) |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with skin irritation in ZYN002 application areas | Skin assessment examination | Up to 33 days |
| Number of participants with abnormal physical examination results | Targeted physical examination | Up to 33 days |
| Number of participants with abnormal clinical laboratory results | Laboratory testing | Up to 33 days |
| Number of participants with abnormal vital sign results | Vital Sign measures | Up to 33 days |
| Number of participants with abnormal continuous pulse oximetry results | Continuous pulse oximeter | Up to 33 days |
| Number of participants with abnormal electrocardiogram (ECG) | 12-lead ECG | Up to 33 days |
References
Clinical Trials Gov: Drug Interaction Study of ZYN002 Transdermal Gel and Probe SubstratesOther trials to consider
Loading suggested trials...
