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Trial registered on ANZCTR


Registration number
ACTRN12613001064796
Ethics application status
Approved
Date submitted
19/09/2013
Date registered
24/09/2013
Date last updated
28/07/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Noribogaine Therapy for Relief of Opioid withdrawal, Phase 1B
Scientific title
A Phase 1B, Single Center, Randomized, Double-Blind, Placebo-Controlled, Ascending Single Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Noribogaine in Opioid Dependent Participants Seeking to Discontinue Methadone Opioid Substitution Treatment (OST)
Secondary ID [1] 282995 0
ZPS-513 (Protocol ID)
Universal Trial Number (UTN)
U1111-1142-3953
Trial acronym
NITROW-P1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Symptoms of opioid withdrawal 289822 0
Condition category
Condition code
Mental Health 290176 290176 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Administration of a single oral dose of noribogaine. It is planned that the first dose cohort will receive 60mg, the second cohort 120mg and the third cohort 180mg. Noribogaine will be administered under supervision at the study site.
Intervention code [1] 287711 0
Treatment: Drugs
Comparator / control treatment
Each study cohort will consist of 9 participants - six randomised to noribogaine and three randomised to placebo (microcrystalline cellulose capsule).
Control group
Placebo

Outcomes
Primary outcome [1] 290210 0
Evaluate the safety and tolerability of noribogaine in opioid dependent participants seeking to discontinue their methadone OST. This will be evaluated by adverse events, vitals signs, ECGs, laboratory tests, physical exam, ocular exam and C-SSRS.
Timepoint [1] 290210 0
Day 7
Primary outcome [2] 290560 0
Evaluate the pharmacokinetics of noribogaine in opioid dependent participants seeking to discontinue their methadone OST. The following pharmacokinetic parameters will be derived for noribogaine: Cmax, AUCT, AUC0-inf8), half-life, Tmax, Vd/F and CL/F. Urine will be assayed for noribogaine and its metabolites.
Timepoint [2] 290560 0
Day 7
Secondary outcome [1] 304111 0
Ability to discontinue methadone OST (Endpoint is time to resumption of OST)
Timepoint [1] 304111 0
Day 7
Secondary outcome [2] 304112 0
Withdrawal Suppression as measured by SOWS, OOWS, COWS, Mood VAS, ASI and PRS rating scales
Timepoint [2] 304112 0
Day 7
Secondary outcome [3] 304113 0
Noribogaine and methadone pharmacodynamics, as measured by oximetry, capnography and pupillometry
Timepoint [3] 304113 0
Day 7
Secondary outcome [4] 304117 0
Methadone Pharmacokinetic Analysis - the following pharmacokinetic parameters will be derived for methadone: Cmax, AUCO24, AUC, AUC0 inf, and half-life, Tmax, Vd/F and CL/F.
Timepoint [4] 304117 0
Day 1

Eligibility
Key inclusion criteria
The main inclusion criteria are opioid dependent male and female adults who provide written consent and are on stable doses of methadone through the OST programme. Participants cannot have any other major illnesses or disorders and must be willing to comply with the restrictions of the study.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria include current treatment for hepatitis C; HIV positive; DSM IV Axis I diagnosis of psychotic disorders; specified excluded concomitant medications; DSM IV criteria for dependence on substances other than opioids, caffeine, and/or nicotine.

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)
After obtaining consent and confirming eligibility, the participant will be enrolled in the study. Randomisation will occur prior to administration of Study Drug on Day 1. Study drug will be prepared for each participant by pharmacy staff, according to the randomisation code. All clinical staff will remain blinded. 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
This is a Phase 1B study and therefore an industry- standard sample of 9 participants per dose cohort has been chosen.

Participant demographic and presenting clinical features will be summarized using standard descriptive statistics, including means, medians, ranges, standard deviations, and frequencies and percentages as appropriate. These summaries will be presented by randomized group.

Adverse events and serious adverse events collected after study drug administration will be listed individually and be summarised by relatedness and severity classes by randomised group. Other safety variables, including laboratory and ophthalmological assessments, C-SSRS responses, vital signs, and ECG data will be summarized at each sampling time after study drug administration for each dose group and placebo, using means, medians, standard deviations and ranges.

Data listings and summaries of the pharmacokinetic parameters by dose level will be presented for the noribogaine PkP and methadone PkP. Descriptive statistics including means, medians, standard deviations and ranges or frequencies and percentages) will be used to summarize these. The pharmacokinetic parameters (Cmax, AUC(0-24), AUC(T), AUC(8), half-life, Tmax, Vd/F and CL/F ) will be estimated using standard non-compartmental models from the noribogaine and methadone plasma concentration data. Cmax, AUC(0-24), AUC(T) and AUC(8) parameters will be dose adjusted (divided by the dose of each group) and compared between groups using ANOVA or Kruskall-Wallis non-parametric ANOVAs as appropriate. These comparisons test the null hypothesis of dose proportionality for each parameter.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 5291 0
New Zealand
State/province [1] 5291 0
Otago

Funding & Sponsors
Funding source category [1] 287775 0
Commercial sector/Industry
Name [1] 287775 0
DemeRx Inc
Address [1] 287775 0
DemeRx, Inc, 305 S. Andrews Avenue, Suite 515 Fort Lauderdale, FL 33301 USA
Country [1] 287775 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
DemeRx Inc
Address
DemeRx, Inc, 305 S. Andrews Avenue, Suite 515 Fort Lauderdale, FL 33301 USA
Country
United States of America
Secondary sponsor category [1] 286502 0
None
Name [1] 286502 0
Address [1] 286502 0
Country [1] 286502 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289725 0
Southern health and Disability Ethics Committee
Ethics committee address [1] 289725 0
Health and Disability Ethics Committees
1 The Terrace
PO Box 5013
Wellington
6011
Ethics committee country [1] 289725 0
New Zealand
Date submitted for ethics approval [1] 289725 0
06/08/2013
Approval date [1] 289725 0
27/08/2013
Ethics approval number [1] 289725 0
13/STH/100

Summary
Brief summary
This is a research study to evaluate the safety, tolerability and effects of noribogaine, an atypical opioid. We will also be looking at its effects on opioid withdrawal symptoms in opioid dependent people who are maintained on stable doses of methadone and who want to stop taking methadone.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 42082 0
Prof Paul Glue
Address 42082 0
Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 913
Dunedin 9016
New Zealand
Country 42082 0
New Zealand
Phone 42082 0
+64 21 243 3372
Fax 42082 0
Email 42082 0
paul.glue@otago.ac.nz
Contact person for public queries
Name 42083 0
Ms Linda Folland
Address 42083 0
Zenith Technology Ltd
156 Frederick Street (P O Box 1777)
Dunedin 9016
Country 42083 0
New Zealand
Phone 42083 0
+64 3 477 9669
Fax 42083 0
Email 42083 0
Linda.Folland@zenithtechnology.co.nz
Contact person for scientific queries
Name 42084 0
Dr John Howes
Address 42084 0
DemeRx, Inc, 305 S. Andrews Avenue, Suite 515

Fort Lauderdale, FL 33301 USA
Country 42084 0
United States of America
Phone 42084 0
+1 954 607 3670
Fax 42084 0
Email 42084 0
howesjf@aol.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary