Drug-drug Interaction Study of Ganaplacide and Lumefantrine With Midazolam, Repaglinide, Dextromethorphan, Metformin, Rosuvastatin and Dolutegravir

Summary

The purpose of this study is to assess the effect of multiple doses of ganaplacide and lumefantrine combination on the substrates of cytochrome P450 (CYP) 3A4 (midazolam), CYP2C8 (repaglinide), CYP2D6 (dextromethorphan), organic cation transporter (OCT) 1, multidrug and toxin extrusion (MATE) 1 (metformin) in Cohort 1 and a substrate of the organic anion transporting polypeptide (OATP) 1B1, OATP1B3 and Breast Cancer Resistance Protein (BCRP) transporter (rosuvastatin) and an antiretroviral drug (dolutegravir) in Cohort 2.

Results from this study will provide guidance on prescribing ganaplacide and lumefantrine combination when co-administered with substrates of the CYP enzymes (CYP3A4, CYP2C8 and CYP2D6) and transporters (OCT1, MATE1, OATP1B1, OATP1B3, and BCRP), and dolutegravir.

Conditions

• Malaria

Interventions

DRUG

Midazolam

Midazolam 2 mg (1 mL of 2 mg/mL oral solution) administered as a single dose in a 4-probe cocktail in the morning in Period 1 on Day 1 and in Period 2 on Day 3.

DRUG

Repaglinide

Repaglinide 0.5 mg (1 x 0.5 mg tablet) administered as a single dose in a 4-probe cocktail in the morning in Period 1 on Day 1 and in Period 2 on Day 3.

DRUG

Dextromethorphan

Dextromethorphan 15 mg (10 mL of 7.5 mg/5 mL syrup) administered as a single dose in a 4-probe cocktail in the morning in Period 1 on Day 1 and in Period 2 on Day 3.

DRUG

Metformin

Metformin 500 mg (1 x 500 mg tablet) administered as a single dose in a 4-probe cocktail in the morning in Period 1 on Day 1 and in Period 2 on Day 3.

DRUG

Ganaplacide

Ganaplacide 400 mg (4 x 100 mg tablets) administered q.d. in Period 2 on Days 1 - 3, with the 4-probe cocktail co administered on the morning of Day 3.

COMBINATION_PRODUCT

Lumefantrine

Lumefantrine 960 mg (4 x 240 mg sachets) administered q.d. on Days 1 - 3, with the 4-probe cocktail (as a single dose) co administered on the morning of Day 3.

DRUG

Rosuvastatin

Rosuvastatin 5 mg (1 x 5 mg tablet) administered as a single dose in a 2-probe cocktail in the morning in Period 1 on Day 1 and in Period 2 on Day 3.

DRUG

Dolutegravir

Dolutegravir 50 mg (1 x 50 mg tablet) administered as a single dose in a 2-probe cocktail in the morning in Period 1 on Day 1 and in Period 2 on Day 3.

DRUG

Ganaplacide

Ganaplacide 400 mg (4 x 100 mg tablets) administered q.d. in Period 2 on Days 1 - 3, with the 2-probe cocktail co administered on the morning of Day 3.

COMBINATION_PRODUCT

Lumefantrine

Lumefantrine 960 mg (4 x 240 mg sachets) administered q.d. on Days 1 - 3, with the 4-probe cocktail (as a single dose) co administered on the morning of Day 3.

Sponsors & Collaborators

• Medicines for Malaria Venture

  collaborator OTHER

• Novartis Pharmaceuticals

  lead INDUSTRY

Principal Investigators

• Novartis Pharmaceuticals · Novartis Pharmaceuticals

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-03-09

Primary Completion

2022-10-17

Completion

2022-10-17

Countries

• United Kingdom

Study Locations