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

Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04233437
• Other study ID #: SAFE2019_01
• Status: Completed
• Phase: Phase 1
• Start date: February 10, 2020
• Est. completion date: May 16, 2020

Study information

• Verified date: September 2020
• Source: Moleac Pte Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: May 16, 2020
• Est. primary completion date: May 16, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Healthy subjects, male or female

2. 18 to 55 years old

3. Body mass index of 18 to <30 kg/m2

4. Able to understand the study requirements and provide written informed consent for participation in the study.

Exclusion Criteria:

1. 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).

2. 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

3. Surgery within 4 weeks prior to Screening, as determined by the Investigator

4. 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).

5. Use of tobacco- or nicotine-containing products within 72 hours prior to dosing.

6. Current substance or alcohol abuse/addiction

7. Women who are pregnant or breastfeeding.

8. 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.

9. 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.

10. Male subjects unless they are willing not to donate sperm 90 days from last study drug administration.

11. 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.

12. 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.

13. 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).

14. Any abnormal physical examination findings or laboratory results (including serum electrolytes such as sodium, potassium and chloride) or abnormal ECG findings (like atrial fibrillation or flutter, supraventricular tachycardia, pre-excitation or wolff Parkinson white. Etc) at screening that is considered to be clinically significant by the study investigator.

15. Any medical condition which, in the study investigator's opinion, may jeopardize the subject by his/her participation in this study, may hamper his/her ability to complete procedures required in the study, or affect the validity of the study results.

16. Administration of an investigational drug (new chemical entity) or device trial within 90 days or 5 half-lives, whichever is longer, prior to the first dose, or concomitant participation in an investigation study involving no drug administration.

Related Conditions & MeSH terms

• Hypersensitivity
• Stroke

Intervention

Drug:
• MLC1501
MLC1501 capsules (4 capcules (2000 mg) twice a day)
• CYP Cocktail
Repaglinide 0.25 mg, caffeine 100 mg, warfarin 10 mg (with vitamin K), omeprazole 40 mg, dextromethorphan 30 mg, midazolam 2 mg
• Transporter Cocktail
Digoxin 0.25 mg, furosemide 1 mg, metformin 10 mg, rosuvastatin 10 mg

Locations

Country	Name	City	State
Australia	Nucleus Network	Melbourne	Victoria

Sponsors (2)

Lead Sponsor	Collaborator
Moleac Pte Ltd.	Moleac Australia Pty Ltd

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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	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.