Drug-Drug Interaction Study of MLC1501 Using Cocktail of Drugs Acting as Sensitive Clinical Probes/Substrates of Cytochrome P450 Isoenzymes and Transporters in Healthy Subjects

NCT04233437 | Completed Phase 1 FDA Drug

• 1 other identifier: SAFE2019_01
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-centre phase I study to assess the Drug-Drug Interaction potential of MLC1501 with a cocktail of drugs acting as sensitive clinical probe substrates of Cytochrome P450 isoenzymes and Transporters in healthy subjects . The study will have 2 cohorts, one for the CYP study and the other for the Transporters study. Eligible subjects (n=24) will be assigned to one of the 2 cohorts in a 1:1 ratio.

Conditions

Stroke

Outcome Measures

Primary Outcomes (3)

• Change in area under curve (AUC) of individual substrates is being assessed between cocktail alone and cocktail + MLC1501 administration

  Assayed in plasma samples collected at various time points after cocktail administration and cocktail + MLC1501 administration.

  Through study completion, an average of 29 days and 18 days for CYP and Transporter cohort, respectively.

• Change in maximum concentration (Cmax) of individual substrates is being assessed between cocktail alone and cocktail + MLC1501 administration

  Assayed in plasma samples collected at various time points after cocktail administration and cocktail + MLC1501 administration.

  Through study completion, an average of 29 days and 18 days for CYP and Transporter cohort, respectively.

• Change in time taken to reach maximum concentration (Tmax) of individual substrates is being assessed between cocktail alone and cocktail + MLC1501 administration

  Assayed in plasma samples collected at various time points after cocktail administration and cocktail + MLC1501 administration.

  Through study completion, an average of 29 days and 18 days for CYP and Transporter cohort, respectively.

Secondary Outcomes (1)

• Ratio of geometric means (GMR) between cocktail alone and cocktail + MLC1501 for the AUC and Cmax of the corresponding probe

  Through study completion, an average of 29 days and 18 days for CYP and Transporter cohort, respectively.

Study Arms (2)

CYP Cohort

EXPERIMENTAL

MLC1501 \& CYP cocktail drugs

Drug: MLC1501; Drug: CYP Cocktail

Transporter Cohort

EXPERIMENTAL

MLC1501 \& Transporter cocktail drugs

Drug: MLC1501; Drug: Transporter Cocktail

Interventions

MLC1501 DRUG

MLC1501 capsules (4 capcules (2000 mg) twice a day)

CYP Cohort; Transporter Cohort

CYP Cocktail DRUG

Repaglinide 0.25 mg, caffeine 100 mg, warfarin 10 mg (with vitamin K), omeprazole 40 mg, dextromethorphan 30 mg, midazolam 2 mg

CYP Cohort

Transporter Cocktail DRUG

Digoxin 0.25 mg, furosemide 1 mg, metformin 10 mg, rosuvastatin 10 mg

Transporter Cohort

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy subjects, male or female
• to 55 years old
• Body mass index of 18 to \<30 kg/m2
• Able to understand the study requirements and provide written informed consent for participation in the study.

You may not qualify if:

• Any history of or presences of medical condition (such as hypertension, diabetes mellitus, hyperlipidaemia, or any cardiac, neurological, pulmonary, gastrointestinal, hepatic, hematologic, or renal disease).
• Concurrent use of any medication to treat any medical condition
• CYP cohort: Within 72hr of the first dose of repaglinide or 5 half-lives of dosing of any medication, whichever longer, and until the end of the study
• Transporter cohort: Within 72hr of first dose of Transporter cocktail or 5 half-lives of dosing of any medication, whichever longer, and until the end of the study
• Surgery within 4 weeks prior to Screening, as determined by the Investigator
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs including cholecystectomy (uncomplicated appendectomy and hernia repair will be allowed).
• Use of tobacco- or nicotine-containing products within 72 hours prior to dosing.
• Current substance or alcohol abuse/addiction
• Women who are pregnant or breastfeeding.
• Women who are of child-bearing potential unless they maintain abstinence during study period or use barrier method of contraception and male partner using condom. Systemically acting hormonal contraceptives are not allowed, however locally acting hormonal contraceptives i.e. intrauterine device (IUD) (including Mirena) is allowed. Menopausal/post-menopausal women without menstruation for 12 consecutive months or surgically sterilized women may also be included. Intake of oral contraceptive pills or hormone replacement therapy is not allowed.
• Male subjects with female partner of child-bearing potential unless they maintain abstinence during study period or use of barrier method of contraception with female partner using any method of contraception.
• Male subjects unless they are willing not to donate sperm 90 days from last study drug administration.
• Use or intend to use any medications or products known to alter drug absorption, metabolism, or elimination processes, vitamin, minerals, herbal/traditional medicines including St John's Wort. 20 days prior to the first dose, unless deemed acceptable by the Investigator.
• Caffeine-containing beverages, substance, alcohol, grapefruit juice/grapefruit containing products, Seville oranges/ juice/, chamomile, liquorice, broccoli or brussels sprouts within the 72hrs prior to dosing.
• Any known hypersensitivity/allergic reaction/anaphylaxis to food, animal stings, drugs inclusive of drugs used in CYP and transporter cocktail in the study /components of MLC1501, or members of the Fabaceae/Leguminosae family (e.g. legume, pea, bean), Polygalaceae family (e.g. milkwort, snakeroot), Apiaceae/ Umbelliferae family (e.g. anise, caraway, carrot, celery, dill, parsley, parsnip), or Quillaja bark (soapbark).

Sponsors & Collaborators

• Moleac Pte Ltd.: lead
• Moleac Australia Pty Ltd: collaborator

Study Sites (1)

Nucleus Network

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be assigned to either CYP or Transporter cohort in ratio of 1:1.

Study Record Dates

• First Submitted: January 10, 2020
• First Posted: January 18, 2020
• Study Start: February 10, 2020
• Primary Completion: May 16, 2020
• Study Completion: May 16, 2020
• Last Updated: September 3, 2020

Record last verified: 2020-09

Locations

AU (1)