NCT05084651

Brief Summary

The study will assess the effect of multiple doses of itraconazole, a strong CYP3A4/5 inhibitor, on the PK of ganaplacide and lumefantrine in healthy participants. This study will provide data that is relevant for advice regarding possible concomitant medications that are inhibitors of CYP3A4/5 in future clinical studies with ganaplacide and lumefantrine and for potential future labeling considerations

Trial Health

87
On Track

Trial Health Score

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

Enrollment
19

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Nov 2021

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

October 6, 2021

Completed
14 days until next milestone

First Posted

Study publicly available on registry

October 20, 2021

Completed
29 days until next milestone

Study Start

First participant enrolled

November 18, 2021

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 13, 2022

Completed
1 day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 14, 2022

Completed
Last Updated

October 28, 2022

Status Verified

October 1, 2022

Enrollment Period

6 months

First QC Date

October 6, 2021

Last Update Submit

October 27, 2022

Conditions

Malaria

Keywords

Drug-drug interactionDDIganaplacidelumefantrineitraconazoleCytochrome P450CYPPharmacokineticPKsafety 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, 3, 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, 3, 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, 3, 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, 3, 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, 3, 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, 3, 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, 3, 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, 3, 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, 3, 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, 3, 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, 3, 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, 3, 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, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)

  • +2 more secondary outcomes

Study Arms (1)

Group 1

EXPERIMENTAL

Each participant will receive a single oral dose of ganaplacide and lumefantrine combination on Day 1 of Period 1. In Period 2, participants will receive itraconazole q.d. on Days 1 to 18 and a single dose of ganaplacide and lumefantrine combination on Day 5, approximately 2 hours after the itraconazole dose

Drug: GanaplacideCombination Product: LumefantrineDrug: Itraconazole

Interventions

GanaplacideDRUG

Treatment A/Period 1: 400 mg (4 x 100 mg tablets) at Hour 0 on Day 1 Treatment B/Period 2: 400 mg (4 x 100 mg tablets) at Hour 0, approximately 2 hours after itraconazole dosing, on Day 5.

Also known as: KAF156
Group 1
LumefantrineCOMBINATION_PRODUCT

Treatment A/Period 1: 480 mg (2 x 240 mg sachets) at Hour 0 on Day 1 Treatment B/Period 2: 480 mg (2 x 240 mg sachets) at Hour 0, approximately 2 hours after itraconazole dosing, on Day 5.

Also known as: LUM566
Group 1
ItraconazoleDRUG

200 mg (20 mL of 10 mg/mL oral solution) q.d. on Days 1 to 18

Group 1

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 to 29.9 kg/m2 inclusive, at Screening.

You may not qualify if:

  • 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 known 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).

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

ganaplacideLumefantrineItraconazole

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

FluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPiperazines

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

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

October 6, 2021

First Posted

October 20, 2021

Study Start

November 18, 2021

Primary Completion

May 13, 2022

Study Completion

May 14, 2022

Last Updated

October 28, 2022

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will not share

Locations

GB(1)