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

Phase 1

Completed

• Conditions: Autism; Mental Health - Autistic spectrum disorders

• Registration Number: ACTRN12620000234910
• Lead Sponsor: Maplight therapeutics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-02-25
• Study Completion: 2020-11-15
• Last Update Posted: 22 November 2021

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 41

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.

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

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.[Self-reported, and emerging adverse events, recorded from the time of screening until the end of the trial.<br>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)<br>Vital signs (performed at Screening, intake, baseline and during the up-titrate, treatment and down-titration period)<br>Electrocardiograms and Physical examinations (performed at Screening, intake, baseline and during the up-titrate, treatment and down-titration period)]

Secondary Outcome Measures

Name	Time	Method
To characterize the pharmacokinetic profile of zolmitriptan after repeat dosing. AUC, Cmax and half-life will be calculated in the pharmacokinetic assessments [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. <br>Cerebrospinal fluid sampling, measured on day 4 of the treatment period <br>];To define the maximum tolerated, three times daily, oral dose of zolmitriptan<br>Maximum tolerated dose will be based on treatment related adverse events[Self reported, or emerging adverse events recorded from screening through to the end of the study]