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Trial registered on ANZCTR


Registration number
ACTRN12620000234910p
Ethics application status
Submitted, not yet approved
Date submitted
29/01/2020
Date registered
25/02/2020
Date last updated
25/02/2020
Date data sharing statement initially provided
25/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
An interventional study to assess the safety, pharmacokinetic (PK, the measure of how the human body processes a substance) response and tolerability (how well a substance is tolerated by participants) to Zolmitriptan following multiple oral doses in Adult Healthy Volunteers
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Study to Assess the Safety, Tolerability and Pharmacokinetic Response of Zolmitriptan Following Multiple Ascending Doses in Adult Healthy Volunteer Subjects.
Secondary ID [1] 300107 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autism 315637 0
Condition category
Condition code
Mental Health 313931 313931 0 0
Autistic spectrum disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Approximately 48 healthy volunteer subjects will be dosed with either Zolmitriptan or placebo, 3 times per day for an up-titration period (gradually increasing the dose by up to 10mg per day depending on the cohort), a 7 day treatment period at the maximum dose intended for that cohort (up to 6 cohorts to be completed), and a down-titration period (gradually decreasing the dose by up to 10mg per day depending on the cohort), with a follow up visit planned for 14 days after dosing has stopped.

A safety review meeting will occur after all subjects have appropriately dosed to determine if the next cohort will begin. If it is determined that the completed cohort was not suitably tolerated, the prior cohort might be repeated with another group of 8 subjects.

Participants will be confined to the clinical unit for the entirety of the dosing period for monitoring.

Zolmitriptan is an oral tablet. The maximum dose administered will be 5mg three times a day (TID) for cohort 1, 10mg TID for cohort 2, 20mg TID for cohort 3, 30mg TID for cohort 4, 40mg TID for cohort 5. The dose for cohort 6 will be determined by the safety committee based on previous cohorts, but will not exceed 40mg TID.

The up-titration, and down-titration period for each cohort will be 2 days for cohort 1, 4 days for cohorts 2 and 3, and 5 days for cohorts 4, 5 and 6.
Intervention code [1] 316394 0
Treatment: Drugs
Comparator / control treatment
The placebo tablets will be made to mimic the appearance of the ZOLTRIP drug product using PROSOLV® EASYtab SP, an all-in-one composite: binder-filler, glidant, superdisintegrant, and lubricant.
Control group
Placebo

Outcomes
Primary outcome [1] 322331 0
To investigate the safety and tolerability of treatment with oral administration of Zolmitriptan, three times a day, versus placebo, based on emerging safety and tolerability data, in healthy adult subjects.
Timepoint [1] 322331 0
Self-reported, and emerging adverse events, recorded from the time of screening until the end of the trial.
Clinical laboratory evaluations of serum chemistry, hematology, urine chemistry and urinalysis from baseline throughout the study (performed at Screening, intake, baseline and during the up-titrate, treatment and down-titration period)
Vital signs (performed at Screening, intake, baseline and during the up-titrate, treatment and down-titration period)
Electrocardiograms and Physical examinations (performed at Screening, intake, baseline and during the up-titrate, treatment and down-titration period)
Secondary outcome [1] 378139 0
To characterize the pharmacokinetic profile of zolmitriptan after repeat dosing. AUC, Cmax and half-life will be calculated in the pharmacokinetic assessments
Timepoint [1] 378139 0
Pharmacokinetic blood samples taken at pre dose, during the up-titration period (once each day from day 1) and at pre-dose and 1, 2, 4, 6 hours post dose during the treatment period.
Cerebrospinal fluid sampling, measured on day 4 of the treatment period
Secondary outcome [2] 379068 0
To define the maximum tolerated, three times daily, oral dose of zolmitriptan
Maximum tolerated dose will be based on treatment related adverse events
Timepoint [2] 379068 0
Self reported, or emerging adverse events recorded from screening through to the end of the study

Eligibility
Key inclusion criteria
1. Healthy adult male and female subjects ages 18 to 45 years (inclusive).
2. Negative screen for drugs of abuse.
3. Body mass index (BMI) 18 through 32 kg/m2, inclusive.
4. Male subjects and female subjects of childbearing potential that are sexually active must practice effective contraception from screening of the study through to 30 days after their last dose of study drug. Effective contraception is the use of two contraception methods, defined as condom use (male and/or female type), hormonal contraception (women) or IUD. This does not apply to participants who are surgically sterilized by bilateral tubal ligation, bilateral oophorectomy, or hysterectomy, or participants who practice sexual abstinence while a research subject in this study, or participants in same-sex relationships.
5. Ability to participate, willingness to give written informed consent, and willingness to comply with the study restrictions.

Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. 1. Have taken, with 4 weeks of Screening or Intake, any of the following:
• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Serotonin-Norepinephrine Reuptake Inhibitor (SNRIs).
• Any MAO-O inhibitor
• Another 5-HT1 agonist, or an ergotamine-containing or ergot-type medication (example: dihydroergotamine or methysergide), including St John’s wort
• Any MAO-A inhibitor
2. Are taking cimetidine and are unable to discontinue use of cimetidine from Screening until the End of Study follow-up.
3. Significant current use of tobacco products, as judged by the Investigator.
4. Have a diagnosis or clinical history of cardiac, cerebrovascular or peripheral vascular disease, including Prinzmetal’s angina and Wolff-Parkinson-White syndrome
5. Screening or Intake systolic blood pressure =180mmHg (confirmed with repeat readings), or a clinical history of uncontrolled or severe hypertension.
6. Evidence of clinically significant ECG abnormalities at Screening or Baseline, in the clinical judgement of the Investigator.
7. Screening or Intake liver function tests that demonstrate an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3X the upper limit of normal.
8. Diagnosed with, or clinical history of epilepsy or structural brain lesions reported at screening.
9. Known history of alcohol use disorder or other substance use disorder within 6 months prior to Screening.
10. Positive screening for human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C virus antibodies at screening.
11. Pregnant or lactating female subjects.
12. History of galactose intolerance (i.e. Lapp lactase deficiency or glucose-galactose malabsorption).
13. Participating in any other study and have received any other investigational medication or device within 30 days prior to screening or are taking part in a non-medication study which, in the opinion of the Investigator, would interfere with the interpretation of the assessments in this study.
14. Other medical or psychiatric condition which, in the opinion of the Investigator, would place the subject at increased risk of safety/tolerability issues and/or would preclude obtaining voluntary consent and/or would confound the interpretation of the primary outcome measures in the study.
15. Unwillingness or inability to comply with the study protocol, (including abstaining from all tobacco products during the dosing period), for any other reason.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
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 in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 15527 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 28894 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 304551 0
Commercial sector/Industry
Name [1] 304551 0
Maplight therapeutics
Address [1] 304551 0
501, 2nd Street
Sanfrancisco, CA
Country [1] 304551 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Maplight therapeutics
Address
501, 2nd Street
Sanfrancisco, CA
Country
United States of America
Secondary sponsor category [1] 304829 0
Commercial sector/Industry
Name [1] 304829 0
Accelagen
Address [1] 304829 0
Suite 1.02, Level 1
722 High Street, Kew East
Victoria, Australia 3102
Country [1] 304829 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 304978 0
Bellberry Limited
Ethics committee address [1] 304978 0
123 Glen Osmond Rd, Eastwood SA 5063
Ethics committee country [1] 304978 0
Australia
Date submitted for ethics approval [1] 304978 0
29/01/2020
Approval date [1] 304978 0
Ethics approval number [1] 304978 0

Summary
Brief summary
The study is investigating the safety, tolerability and pharmacokinetics of multiple ascending doses of the already approved drug Zolmitriptan in 48 adult healthy volunteer subjects, for the potential treatment of people with Austism spectrum disorders.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98838 0
Dr Jason Lickliter
Address 98838 0
Nucleus Network, Level 5, Burnet Building AMREP Precinct, 89 Commercial Road, Melbourne VIC 3000
Country 98838 0
Australia
Phone 98838 0
+61 3 90768960
Fax 98838 0
Email 98838 0
j.lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 98839 0
Mr Greg Plunkett
Address 98839 0
Accelagen
Suite 1.02, Level 1
722 High Street, Kew East
Victoria, Australia 3102
Country 98839 0
Australia
Phone 98839 0
+61410552020
Fax 98839 0
Email 98839 0
greg.plunkett@accelagen.com.au
Contact person for scientific queries
Name 98840 0
Dr James Lillie
Address 98840 0
Maplight
501 2 Nd Street
San Francisco, CA, 94107
Phone: 919-641-8778
Country 98840 0
United States of America
Phone 98840 0
+1 617 763 6511
Fax 98840 0
Email 98840 0
jlillie@maplightrx.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Study outcomes are reported as the total population, and not based on individual results.
What supporting documents are/will be available?
Clinical study report
How or where can supporting documents be obtained?
Type [1] 6575 0
Clinical study report
Citation [1] 6575 0
Link [1] 6575 0
Email [1] 6575 0
Other [1] 6575 0
Upon request from local sponsor (email: greg.plunkett@accelagen.com.au)
Attachment [1] 6575 0
Summary results
No Results