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Trial registered on ANZCTR


Registration number
ACTRN12622000133730
Ethics application status
Approved
Date submitted
11/01/2022
Date registered
27/01/2022
Date last updated
27/01/2022
Date data sharing statement initially provided
27/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative assessment of the absorption of a generic formulation of (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol transdermal patch against the innovator (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol transdermal patch conducted under fasting conditions with the inclusion of a naltrexone block in healthy male and female volunteers
Scientific title
A single dose, randomized, open label, bioequivalence study of a test formulation of (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol transdermal patch in a 2 way crossover comparison against the innovator (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol transdermal patch conducted under fasting conditions with the inclusion of a naltrexone block in healthy male and female volunteers
Secondary ID [1] 306169 0
None
Universal Trial Number (UTN)
U1111-1262-5285
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
(2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol is a partial opioid agonist indicated for the management of severe pain. 324878 0
Condition category
Condition code
Anaesthesiology 322314 322314 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single dose, crossover study design whereby each participant receives the test formulation of (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol (1 x 40 mcg/hr) on one occasion and the innovator formulation of (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol (1 x 40 mcg/hr) on one occasion with the inclusion of a naltrexone block given prior to patch application, at application, 12 hours after patch application, then once every 24 hours while the patch is in place to reduce side effects.

Each naltrexone dose will be a 50 mg oral tablet.

Each (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol dosing will be seperated by a two week washout period. The intervention for this trial is the test formulation of (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol .

No water is allowed for 1 hour prior to dosing until 1 hour after dosing (except for the water consumed with the dose).

Participants are required not to eat for 10 hours before receiving each dose and to fast for approximately 4 hours after receiving each dose. Bathroom visits will be supervised to ensure no unauthorised water or food intake and for personal safety. Participants will be confined at the Clinical Site for 12 hours prior to dosing to ensure compliance and will be monitored and for 24 hours after dosing.

Standard meals will be consumed at the Clinical Site with no additional food intake allowed. Alcohol breath testing will be performed upon each participant reporting to the Clinical Site 12 hours prior to dosing.

Pre and post study laboratory tests will be completed to assess the health of participants along with HIV, Hepatitis and drugs of abuse testing.

Each (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol patch will be applied to the upper arm. Investigators will examine every subject to ensure the patch has been applied correctly.

Each dose of naltrexone will be taken orally with 240 ml of water at ambient temperature. Medication must be swallowed whole and a mouth check will be conducted to ensure the medication has been taken as directed.
Intervention code [1] 322576 0
Treatment: Drugs
Comparator / control treatment
Single dose, crossover study design whereby each participant receives the test formulation of (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol (1 x 40 mcg/hr) on one occasion and the innovator formulation of (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol (1 x 40 mcg/hr) on one occasion with each dose seperated by a two week washout period. The comparator/control for this trial is the innovator formulation of (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol .
Control group
Active

Outcomes
Primary outcome [1] 330078 0
To compare the bioavailability of (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol (as summarised by Cmax and AUC). All plasma samples will be assayed for (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-olusing one fully validated Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method. Validation will be conducted to comply with EU and FDA guidelines.
Timepoint [1] 330078 0
0 (pre-dose) and at 1, 4, 6, 10, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 176, 192, 200, 216, 224, 240 and 264 hours post dosing.
Secondary outcome [1] 404812 0
Time to maximum peak concentration (Tmax) will be determined by plasma sample analysis. Tmax will be the time where the maximum concentration occurred in the sample points.
Timepoint [1] 404812 0
0 (pre-dose) and at 1, 4, 6, 10, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 176, 192, 200, 216, 224, 240 and 264 hours post dosing.

Eligibility
Key inclusion criteria
Healthy male and non-pregnant females
Aged between 18 and 55
Non-smoker
BMI between 18 and 32 inclusive
Normal, healthy individuals as determined by medical history, physical examination, ECG, blood pressure and laboratory tests
Able to provide written informed consent
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Any history of recent recurrent attacks of bronchitis, asthma, migraine headaches
Concomitant drug therapy of any kind
Sensitivity to (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol or any other similar class of medicines, or the excipients of (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol.
Sensitivity to naltrexone or any other similar class of medicines, or the excipients of naltrexone
History of any conditions that might interfere with the absorption, distribution, metabolism or excretion of the drug
Females who are pregnant and/or are breastfeeding
Smoker (anyone who has smoked in the last 6 months)
History of alcohol or drug abuse or dependency
Participation in a drug study within 60 days of the start of the study or donated blood in the 60 days preceding the study.
Volunteers for whom the Clinical Investigator believes, for any reason, that participation would not be an acceptable risk

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The subject ID will be used to randomise each participant onto the study. Allocation concealment will be completed by the pharmacy staff who are independent of subject recruitment and who are unaware of the identity of each subject.

All staff obtaining consent and confirming eligibility will remain blinded as to what formulation each subject ID has been allocated. Individual randomisation envelopes will be provided in case the identity of study drug administered to a participant needs to be known.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization by computer
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-equivalence
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
12/02/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
26
Accrual to date
Final
Recruitment outside Australia
Country [1] 24490 0
New Zealand
State/province [1] 24490 0
Otago

Funding & Sponsors
Funding source category [1] 310514 0
Commercial sector/Industry
Name [1] 310514 0
Juno Pharmaceuticals Pty Ltd
Country [1] 310514 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corporation Limited
Address
PO Box 1777
156 Frederick St
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 311680 0
None
Name [1] 311680 0
Address [1] 311680 0
Country [1] 311680 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310139 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 310139 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 310139 0
New Zealand
Date submitted for ethics approval [1] 310139 0
11/11/2021
Approval date [1] 310139 0
06/12/2021
Ethics approval number [1] 310139 0
2021 FULL 11157

Summary
Brief summary
The objective of this study is to evaluate the bioequivalence of the test (new) formulation of 1 x 40 mcg/hr against the reference formulation (innovator brand of 1 x 40 mcg/hr (2S)-2-[17-(cyclopropylmethyl)-4, 5a-epoxy-3-hydroxy-6-methoxy-6a, 14-ethano-14a-morphinan-7a-yl]-3, 3-dimethylbutan-2-ol transdermal patch) following oral administration of a multiple dose of 50 mcg/hr of a naltrexone block in healthy male and female subjects under fasting conditions and at steady state.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116614 0
Dr Noelyn Hung
Address 116614 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 116614 0
New Zealand
Phone 116614 0
+64 21 482 148
Fax 116614 0
Email 116614 0
noelyn.hung@otago.ac.nz
Contact person for public queries
Name 116615 0
Mrs Linda Folland
Address 116615 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 116615 0
New Zealand
Phone 116615 0
+64 3 477 9669
Fax 116615 0
Email 116615 0
linda.folland@zenithtechnology.co.nz
Contact person for scientific queries
Name 116616 0
Dr Tak Hung
Address 116616 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 116616 0
New Zealand
Phone 116616 0
+64 3 477 9669
Fax 116616 0
Email 116616 0
tak.hung@zenithtechnology.co.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All data will be compiled into a final report that is the property of the sponsor company


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.