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

A Phase I, Open-label, Fixed-sequence, Two-period, Crossover, Drug-drug Interaction Study to Evaluate the Effect of Multiple Doses of Ganaplacide and Lumefantrine Combination on the Pharmacokinetics of Midazolam, Repaglinide, Dextromethorphan, Metformin, Rosuvastatin and Dolutegravir in Healthy Participants

ClinicalTrials.gov Identifier: NCT05236530

Novartis Reference Number: CKAF156A2104

Last Update: Sep 06, 2022

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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.

Condition 
Malaria
Phase 
Phase 1
Overall status 
Recruiting
Start date 
Mar 09, 2022
Completion date 
Sep 09, 2022
Gender 
All
Age(s)
18 Years - 55 Years (Adult)

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.

Eligibility Criteria

Key Inclusion Criteria:

Signed informed consent must be obtained prior to participation in the study.
Healthy male and non-childbearing potential female participants 18 to 55 years of age inclusive, at Screening.
In good health as determined by medical history, physical examination, vital signs, ECG and clinical laboratory tests at Screening.
Must weigh at least 50 kg with a body mass index (BMI) within the range of 18.0 to 29.9 kg/m2 inclusive, at Screening.

Key Exclusion Criteria:

Use of other investigational drugs within 5 half-lives or 30 days prior to first dosing of study treatment, whichever is longer.
Known family history or presence of long QT syndrome.
Known history or current clinically significant arrhythmias.
History or presence of malignancy of any organ system (other than treated localized basal cell or squamous cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within 5 years of Screening, regardless of whether there is evidence of local recurrence or metastases.
History or presence of duodenal ulcer, ulcerative colitis or Crohn's disease.
Presence of active or uncontrolled thyroid disease.
Has had cholecystectomy (gallbladder removed). Other protocol-defined inclusion/exclusion criteria may apply.

Study Locations

United Kingdom
Novartis Investigative Site
Recruiting
Belfast, BT9 6AD
Northern Ireland
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals

Have a question?

Call 1-888-669-6682 or email [email protected]