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

• Status: Not yet recruiting
• Trial end date: 2022-05-16
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Collaborator: Medicines for Malaria Venture
• Treatments: Dextromethorphan; Dolutegravir; Lumefantrine; Metformin; Midazolam; Repaglinide; Rosuvastatin Calcium

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.