NCT05330273

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
14

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Apr 2022

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 8, 2022

Completed
7 days until next milestone

First Posted

Study publicly available on registry

April 15, 2022

Completed
13 days until next milestone

Study Start

First participant enrolled

April 28, 2022

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 22, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 22, 2022

Completed
Last Updated

January 12, 2023

Status Verified

January 1, 2023

Enrollment Period

7 months

First QC Date

April 8, 2022

Last Update Submit

January 11, 2023

Conditions

Malaria

Keywords

Drug-drug interactionDDIganaplacidelumefantrineefavirenzPharmacokineticPKsafety and tolerabilityhealthy participants

Outcome Measures

Primary Outcomes (8)

  • Observed maximum plasma concentration (Cmax) for Ganaplacide and Lumefantrine

    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.

    0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

  • Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) for Ganaplacide and Lumefantrine

    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.

    0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

  • Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) for Ganaplacide and Lumefantrine

    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUCinf will be listed and summarized using descriptive statistics.

    0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

  • Area under the concentration-time curve from time zero (pre-dose) to the 24-hour time point (AUC^0-24) for Ganaplacide and Lumefantrine

    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC\^0-24 will be listed and summarized using descriptive statistics.

    0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

  • Time of maximum observed drug concentration occurrence (Tmax) for Ganaplacide and Lumefantrine

    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.

    0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

  • Apparent total body clearance of drug from plasma following extravascular administration (CL/F) for Ganaplacide and Lumefantrine

    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL/F will be listed and summarized using descriptive statistics

    0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

  • Apparent volume of distribution during terminal elimination phase following extravascular administration (Vz/F) for Ganaplacide and Lumefantrine

    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz/F will be listed and summarized using descriptive statistics.

    0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

  • Terminal elimination half-life (T^1/2) for Ganaplacide and Lumefantrine

    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. T\^1/2 will be listed and summarized using descriptive statistics.

    0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

Secondary Outcomes (7)

  • Observed maximum plasma concentration (Cmax) for Ganaplacide metabolites (RHF218 and GOU089)

    0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

  • Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) for Ganaplacide metabolites (RHF218 and GOU089)

    0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

  • Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) for Ganaplacide metabolites (RHF218 and GOU089)

    0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

  • Area under the concentration-time curve from time zero (pre-dose) to the 24-hour time point (AUC0-24) for Ganaplacide metabolites (RHF218 and GOU089)

    0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

  • Time of maximum observed drug concentration occurrence (Tmax) for Ganaplacide metabolites (RHF218 and GOU089)

    0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

  • +2 more secondary outcomes

Study Arms (1)

Period 1: KAF156 + LUM566 / Period 2: KAF156 + LUM566 + Efavirenz

EXPERIMENTAL

Participants enrolled will receive a single oral dose of ganaplacide and lumefantrine combination on Day 1 of Period 1. In Period 2, participants will receive an oral dose of efavirenz q.d. in the evening on Days 1 through 24 and a single dose of ganaplacide and lumefantrine combination on the morning of Day 11.

Drug: GanaplacideCombination Product: LumefantrineDrug: Efavirenz

Interventions

GanaplacideDRUG

Period 1: 400 mg (4 x 100 mg tablets) for oral administration Period 2: 400 mg (4 x 100 mg tablets) for oral administration

Also known as: KAF156
Period 1: KAF156 + LUM566 / Period 2: KAF156 + LUM566 + Efavirenz
LumefantrineCOMBINATION_PRODUCT

Period 1: 480 mg (2 x 240 mg sachets) for oral administration Period 2: 480 mg (2 x 240 mg sachets) for oral administration

Also known as: LUM566
Period 1: KAF156 + LUM566 / Period 2: KAF156 + LUM566 + Efavirenz
EfavirenzDRUG

Period 2: 600 mg (1 x 600 mg tablet) for oral administration once daily (q.d.)

Period 1: KAF156 + LUM566 / Period 2: KAF156 + LUM566 + Efavirenz

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • Known family history or presence of long QT syndrome.
  • Known history or current clinically significant arrhythmias.
  • Any single parameter of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), or alkaline phosphatase (ALP) exceeding 1.2 x upper limit of normal (ULN) and total bilirubin ≥ 1.5 x ULN or any elevation above ULN of more than one parameter of ALT, AST, GGT, ALP, or serum bilirubin at Screening or First Baseline.
  • History of psychiatric illness.
  • Score "yes" on item 4 or item 5 of the suicidal ideation section of the C-SSRS, if this ideation occurred in the past 6 months of Screening, or "yes" on any item of the suicidal behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the suicidal behavior section), if this behavior occurred in the past 2 years of Screening.
  • History or presence of seizures.
  • History or presence of duodenal ulcer, ulcerative colitis or Crohn's disease.
  • Presence of active or uncontrolled thyroid disease.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Novartis Investigative Site

Belfast, Northern Ireland, BT9 6AD, United Kingdom

Location

MeSH Terms

Conditions

Malaria

Interventions

ganaplacideLumefantrineefavirenz

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

FluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 8, 2022

First Posted

April 15, 2022

Study Start

April 28, 2022

Primary Completion

November 22, 2022

Study Completion

November 22, 2022

Last Updated

January 12, 2023

Record last verified: 2023-01

Locations

GB(1)