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MalariaPhase 1NCT05084651

Drug-drug Interaction Study of Ganaplacide and Lumefantrine With Itraconazole

A Phase 1 study testing Ganaplacide, Lumefantrine and Itraconazole in people with Malaria, run by Novartis Pharmaceuticals at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Malaria
What is being tested?
Ganaplacide, Lumefantrine and Itraconazole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteUnited Kingdom
Study dates
18 Nov 2021to 14 May 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
  • Other protocol-defined inclusion/exclusion criteria may apply.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • Novartis Investigative Site

    Belfast, Northern Ireland, BT9 6AD

Other trials in United Kingdom

About this study

Official title: A Phase I, Open-label, Fixed Sequence, Two-period, Crossover, Drug-drug Interaction Study to Investigate the Interaction Potential of Itraconazole on the Pharmacokinetics of Ganaplacide and Lumefantrine Combination in Healthy Participants

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

Read the 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 itraconazole on the single dose PK of ganaplacide and lumefantrine in healthy participants.

The study will consist of a screening period of up to 28 days, 2 Baseline evaluations (on Day -1 of each treatment period), and 2 treatment periods which are separated by a washout period. Participants who meet the eligibility criteria at Screening will be admitted to the study site for First Baseline evaluations on Day -1 of Period 1. Baseline safety assessments will be performed prior to first dosing of study treatment in each period.

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 itraconazole once daily (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. There will be 336 hours of sequential blood sampling for PK assessment starting after ganaplacide and lumefantrine dosing in each treatment period. Between the 2 treatment periods, there will be an additional 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.

Each dose of ganaplacide and lumefantrine combination will be administered after at least 10 hours of overnight fasting and will be followed by at least 4 hours of fasting post dose. In Period 2, itraconazole will be administered after at least 10 hours of overnight fasting and followed by at least 1 hour of fasting post dose (except on Day 5 when ganaplacide and lumefantrine will be administered approximately 2 hours after itraconazole dosing and participants will continue fasting for at least 4 hours post ganaplacide and lumefantrine dosing).

Safety assessments (including physical examinations, electrocardiograms (ECGs), vital signs, clinical laboratory evaluations [hematology, chemistry, coagulation, and urinalysis], and adverse event [AE] and serious adverse event [SAE] monitoring) will be performed during the study.

The Study Completion evaluations will occur on Day 19 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. In the case of early termination, Study Completion evaluations will be conducted prior to discharge from the study.

Conditions
Malaria
Being tested
Ganaplacide, Lumefantrine, Itraconazole
Keywords
Drug-drug interaction, DDI, ganaplacide, lumefantrine, itraconazole, Cytochrome P450, CYP, Pharmacokinetic, PK, safety and tolerability, healthy participants
Medical subject headings
Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GanaplacideDrug

    Also called KAF156

    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.

  • LumefantrineCombination product

    Also called LUM566

    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.

  • ItraconazoleDrug

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

Study groups in NCT05084651
Study groupRoleWhat they receive
Group 1ExperimentalEach 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
Receives: Drug: Ganaplacide; Combination Product: Lumefantrine; Drug: Itraconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

  3. 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.

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

  4. 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.

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

  5. 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.

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

  6. 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.

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

  7. 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.

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

  8. 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.

    Measured: 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)
  1. Observed maximum plasma concentration (Cmax) for Ganaplacide metabolites (RHF218 and GOU089)

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

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

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

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

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

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

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

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

  4. 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)

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

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

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

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

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

  6. Terminal elimination half-life (T^1/2) for Ganaplacide metabolites (RHF218 and GOU089)

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

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

  7. Metabolite to Parent Ratio (MR) for Ganaplacide metabolites (RHF218 and GOU089)

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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2021
  2. Study start18 Nov 2021
  3. Primary completion13 May 2022
  4. Study completion14 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05084651
Sponsor's protocol ID
CKAF156A2105
Other IDs
2021-000924-36
Status last verified
Oct 2022
First submitted
6 Oct 2021
Last updated
28 Oct 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ganaplacide, Lumefantrine and Itraconazole in people with Malaria, run by Novartis Pharmaceuticals at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Observed maximum plasma concentration (Cmax) for Ganaplacide and Lumefantrine (time frame: 0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2022.

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