NCT05330273

Drug-drug Interaction Study of Ganaplacide and Lumefantrine With Efavirenz

A Phase I, Open-label, Fixed-sequence, Two-period, Crossover, Drug-drug Interaction Study to Investigate the Effect of Efavirenz on the Pharmacokinetics of Ganaplacide and Lumefantrine Combination in Healthy Participants

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

This study assessed the effect of multiple doses of a moderate inducer of cytochrome P450 (CYP) 3A4 (efavirenz) on the pharmacokinetics (PK) of ganaplacide and lumefantrine combination. Results from this study will provide guidance on prescribing ganaplacide and lumefantrine combination when co-administered with moderate inducers of CYP3A4.

Detailed description

This is an open-label, fixed-sequence, 2-period, crossover, Drug-drug interaction (DDI) study, to evaluate the effect of multiple doses of efavirenz on the single-dose PK of ganaplacide and lumefantrine in healthy participants. The study consisted of a screening period of up to 28 days, 2 Baseline evaluations (on Day 1 of each treatment period), and 2 treatment periods which were separated by a washout period. Participants who meet the eligibility criteria at Screening were admitted to the study site for First Baseline evaluations on Day -1 of Period 1. Baseline safety assessments were performed prior to first dosing of study treatment in each period. The participants were domiciled from the First Baseline visit until the end of the PK sampling in Period 1 and were released from the site. Participants returned to the site for the Second Baseline visit and were domiciled until the Study Completion visit in Period 2. Participants enrolled received a single oral dose of ganaplacide and lumefantrine combination under fasting conditions on Day 1 of Period 1. In Period 2, participants received an oral dose of efavirenz q.d. under fasting conditions in the evening on Days 1 through 24 and a single dose of ganaplacide and lumefantrine combination under fasting conditions on the morning of Day 11. Between the two treatment periods, there was a washout period of at least 14 days, beginning from the last PK sample collection in Period 1 and continuing until the first dose of study treatment in Period 2. Safety assessments (including physical examinations, ECGs, vital signs, clinical laboratory evaluations, C-SSRS, and AE and SAE monitoring) were performed during the study. The Study Completion evaluations occurred on Day 25 of Period 2, followed by a post-study safety contact (e.g. follow-up telephone call, email) approximately 30 days after the last dose of study treatment. Total duration of study was approximately 55 days from the First Baseline visit to the Study Completion visit.

Conditions

• Malaria

Interventions

Type	Name	Description
DRUG	Ganaplacide	Period 1: 400 mg (4 x 100 mg tablets) for oral administration Period 2: 400 mg (4 x 100 mg tablets) for oral administration
COMBINATION_PRODUCT	Lumefantrine	Period 1: 480 mg (2 x 240 mg sachets) for oral administration Period 2: 480 mg (2 x 240 mg sachets) for oral administration
DRUG	Efavirenz	Period 2: 600 mg (1 x 600 mg tablet) for oral administration once daily (q.d.)

Timeline

• Start date: 2022-04-28
• Primary completion: 2022-11-22
• Completion: 2022-11-22
• First posted: 2022-04-15
• Last updated: 2023-01-12

Locations

1 site across 1 country: United Kingdom