This study is an open-label drug-drug interaction (DDI) study of ZYN002 transdermal gel and multiple drugs.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
29
CMAX Clinical Research
Adelaide, South Australia, Australia
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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Time frame: Days 18-21 (Period 3)
Ae0-12 of VPA and metabolites
Urine samples collected over a 12-hour period.
Time frame: 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.
Time frame: Day 17 (Period 2), Days 18 and 20 (Period 3)
Number of participants with skin irritation in ZYN002 application areas
Skin assessment examination
Time frame: Up to 33 days
Number of participants with abnormal physical examination results
Targeted physical examination
Time frame: Up to 33 days
Number of participants with abnormal clinical laboratory results
Laboratory testing
Time frame: Up to 33 days
Number of participants with abnormal vital sign results
Vital Sign measures
Time frame: Up to 33 days
Number of participants with abnormal continuous pulse oximetry results
Continuous pulse oximeter
Time frame: Up to 33 days
Number of participants with abnormal electrocardiogram (ECG)
12-lead ECG
Time frame: Up to 33 days