Piperaquine Granule Formulation Relative Bioavailability and Food Effect Study in Healthy Volunteers.

NCT05930782 | Completed Phase 1 Results

• 1 other identifier: MMV_SMC_22_01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This trial aims to characterise the pharmacokinetic (PK) profile and estimate drug exposure of a single oral dose of piperaquine (PQP) in a dispersible granule formulation compared to the PQP hard tablet formulation in the fasted state (Part 1), to advise the selection of dose when the PQP granule formulation is administered in a fed state in healthy adult participants. Part 2 will assess the effect on different types of meal composition on the PK of a single dose of PQP granule formulation in healthy adult participants.

Conditions

Malaria

Keywords

Pharmacokinetics; Malaria prevention; Bioavailability; Malaria; Food effect; Oral granule formulation

Outcome Measures

Primary Outcomes (5)

• Relative Bioavailability (Frel) of the Maximum Observed Plasma Concentration (Cmax) of the PQP Dispersible Granule Compared to the PQP Hard Tablet in the Fasted State (Frel Cmax).

  Blood samples are analysed for PQP concentrations at the indicated time points to determine the maximum observed plasma concentration (Cmax) for PQP dispersible granule (test) and PQP hard tablet (reference) in the fasted state. Pharmacokinetic parameters are determined using standard non-compartmental analysis. Frel Cmax is calculated as the (%) ratio of Cmax of the PQP dispersible granule compared to the PQP hard tablet in the fasted state.

  Plasma samples taken pre-dose -0.5 hours, then 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, Day 5, Day 8, Day 15, Day 22 and Day 30 post-dose.

• Relative Bioavailability (Frel) of the Area Under the Plasma Concentration-time Curve From Time Zero to 72h Hours (AUC0-72h) of the PQP Dispersible Granule Compared to the PQP Hard Tablet in the Fasted State (Frel AUC0-72h).

  Blood samples are analysed for PQP concentrations at the indicated time points to calculate the area under the plasma concentration-time curve from time zero to 72 hours (AUC0-72h) for PQP dispersible granule (test) and PQP hard tablet (reference) in the fasted state. Pharmacokinetic parameters are determined using standard non-compartmental analysis. Frel AUC0-72h is calculated as the ratio of AUC0-72h of the PQP dispersible granule compared to the PQP hard tablet in the fasted state.

  Plasma samples taken pre-dose -0.5 hours, then 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, Day 5, Day 8, Day 15, Day 22 and Day 30 post-dose.

• Relative Bioavailability (Frel) of the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of the PQP Dispersible Granule Compared to the PQP Hard Tablet in the Fasted State (Frel AUC0-t).

  Blood samples are analysed for PQP concentrations at the indicated time points to calculate the area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t) for PQP dispersible granule (test) and PQP hard tablet (reference) in the fasted state. Pharmacokinetic parameters are determined using standard non-compartmental analysis. Frel AUC0-t is calculated as the ratio of AUC0-t of the PQP dispersible granule compared to the PQP hard tablet in the fasted state.

  Plasma samples taken pre-dose -0.5 hours, then 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, Day 5, Day 8, Day 15, Day 22 and Day 30 post-dose.

• Relative Bioavailability (Frel) of the Area Under the Plasma Concentration-time Curve From Time Zero to 168 Hours (AUC0-168h) of the PQP Dispersible Granule Compared to the PQP Hard Tablet in the Fasted State (Frel AUC0-168h.

  Blood samples are analysed for PQP concentrations at the indicated time points to calculate the area under the plasma concentration-time curve from time zero to 168 hours (AUC0-168h) for PQP dispersible granule (test) and PQP hard tablet (reference) in the fasted state. Pharmacokinetic parameters are determined using standard non-compartmental analysis. Frel AUC0-168h is calculated as the ratio of the AUC0-168h of the PQP dispersible granule compared to the PQP hard tablet in the fasted state.

  Plasma samples taken pre-dose -0.5 hours, then 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, Day 5, Day 8, Day 15, Day 22 and Day 30 post-dose.

• Relative Bioavailability (Frel) of the Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of the PQP Dispersible Granule Compared to the PQP Hard Tablet in the Fasted State (Frel AUC0-∞).

  Blood samples are analysed for PQP concentrations at the indicated time points to calculate the area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-∞) for PQP dispersible granule (test) and PQP hard tablet (reference) in the fasted state. Pharmacokinetic parameters are determined using standard non-compartmental analysis. Frel AUC0-∞ is calculated as the ratio of the AUC0-∞ of the PQP dispersible granule compared to the PQP hard tablet in the fasted state.

  Plasma samples taken pre-dose 0.5 hours, then 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, Day 5, Day 8, Day 15, Day 22 and Day 30 post-dose.

Study Arms (5)

Part 1 (Fasted): Group 1: Piperaquine hard tablets

ACTIVE COMPARATOR

Participants received a single oral dose of Piperaquine hard tablets 320mg (administered in fasting condition of at least 10 hours) (N=12) Piperaquine: Piperaquine tetraphosphate hard tablets 320mg

Drug: Piperaquine Tetraphosphate uncoated tablets

Part 1 (Fasted): Group 2: Piperaquine dispersible granules

EXPERIMENTAL

Participants received a single oral dose of Piperaquine dispersible granule 320mg (administered in fasting condition of at least 10 hours) (N=12) Piperaquine: Piperaquine tetraphosphate dispersible granules 320mg

Drug: Piperaquine Tetraphosphate dispersible granules

Part 2 (Fed): Group 3: Piperaquine dispersible granules

EXPERIMENTAL

Participants received a single oral dose of Piperaquine dispersible granule 320mg administered with a high-fat meal (N=12) Piperaquine: Piperaquine tetraphosphate dispersible granules 320mg

Drug: Piperaquine Tetraphosphate dispersible granules

Part 2 (Fed): Group 4: Piperaquine dispersible granules

EXPERIMENTAL

Participants received a single oral dose of Piperaquine dispersible granule 320mg administered with a low-fat meal representative of African diet. (N=12) Piperaquine: Piperaquine tetraphosphate dispersible granules 320mg

Drug: Piperaquine Tetraphosphate dispersible granules

Part 2 (Fed): Group 5: Piperaquine dispersible granules

EXPERIMENTAL

Participants received a single oral dose of Piperaquine dispersible granule 320mg administered with whole milk (250ml) (N=12) Piperaquine: Piperaquine tetraphosphate dispersible granules 320mg

Drug: Piperaquine Tetraphosphate dispersible granules

Interventions

Piperaquine Tetraphosphate uncoated tablets DRUG

Piperaquine tetraphosphate hard tablet 320 mg; single dose (320 mg) given orally with 240 ml of water

Part 1 (Fasted): Group 1: Piperaquine hard tablets

Piperaquine Tetraphosphate dispersible granules DRUG

Piperaquine tetraphosphate dispersible granules 320 mg dose equivalent dispersed in 25 ml of water; single dose (320 mg) given orally

Part 1 (Fasted): Group 2: Piperaquine dispersible granules; Part 2 (Fed): Group 3: Piperaquine dispersible granules; Part 2 (Fed): Group 4: Piperaquine dispersible granules; Part 2 (Fed): Group 5: Piperaquine dispersible granules

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must fulfil all of the following criteria to be eligible for enrolment in this trial:
• Female or Male aged ≥18 years to ≤55 years at the date of signing informed consent.
• Ability to provide written, personally signed, and dated informed consent to participate in the trial, in accordance with the ICH Good Clinical Practice (GCP) and applicable regulations, before any trial-related procedures.
• An understanding, ability, and willingness to fully comply with trial procedures and restrictions.
• Female participants must agree to follow contraceptive requirements as indicated in Section 13.2.2, from at least 30 days prior to first dosage to 16 weeks after last dosage.
• Agrees not to donate sperm or ova from the time of the first administration of trial medication until twelve weeks after the end of the systemic exposure of the trial drug.
• Participants must have a body weight of 50 kg or greater and a BMI between 18.0 kg/m² - 30.0 kg/m² (inclusive) at screening.
• Satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by; medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG) and clinical laboratory evaluation that is reasonably likely to interfere with the participant's participation in or ability to complete the trial as assessed by the Investigator.

You may not qualify if:

• Participants will be excluded from enrolment in this trial if they fulfil any of the criteria below:
• Prior screen failure or randomisation in this trial. NOTE: Participants who initially failed due to temporary non-medically significant issues are eligible for re-screening once the cause has resolved.
• Female participant who is pregnant (from history, examination or confirmed by a positive serum pregnancy test at screening and/or on Day -1) or breastfeeding.
• Male participants with a female partner(s) who is (are) pregnant or lactating at screening and/or on Day -1, or is (are) expected to be during the trial period.
• Has a mental incapacity or language barriers precluding adequate understanding, co-operation, or compliance with the trial requirements.
• Unable or unwilling to follow a standardised diet and meal schedule or unable to fast, as required during the trial.
• Has milk intolerance.
• Unable to swallow tablets.
• Has veins on either arm that are unsuitable for intravenous puncture or cannulation (e.g., veins that are difficult to locate, or a tendency to rupture during puncture).
• Known or suspected intolerance or hypersensitivity to the investigational products, any closely related compound, or any of the stated ingredients.
• History of significant allergic reaction (e.g., anaphylaxis, angioedema) to any product (food, pharmaceutical, etc) but excluding untreated, asymptomatic, seasonal allergies.
• Donated blood or blood products (excluding plasma) within 90 days prior to trial medication administration.
• Has received or plans to receive a COVID-19 vaccination within two weeks before to one week after trial last visit.
• Treated with medication containing PQP within 90 days or five half-lives preceding the dose of trial medication (whichever is the longer).
• Ingested herbal remedies or dietary supplements containing St. John's Wort in the 30 days before the planned Day 1 of the dosing Part.

Sponsors & Collaborators

• Medicines for Malaria Venture: lead

Study Sites (1)

Ifakara Health Institute (IHI), Bagamoyo Research and Training Centre (BRTC)

Bagamoyo, Bagamoyo District, Pwani Region, Tanzania

Location

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Limitations and Caveats

Participant# 122, results for all collected samples were below the lower limit of quantification (LLOQ) and no PK parameters could be generated. So, data from Participant# 122 was not included in the summary statistics.

Results Point of Contact

• Title: Dr Anne Claire Marrast
• Organization: MMV Medicines for Malaria Venture

marrasta@mmv.org

+41 22 555 03 00

Study Officials

• Florence A Milando, MD, MPH

  Ifakara Health Institute (IHI), Tanzania

  PRINCIPAL INVESTIGATOR

• Said A Jongo, MD, MMed, PhD

  Ifakara Health Institute (IHI), Tanzania

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Part 1: PQP tablet / dispersible granule administered in fasting condition of at least 10 hours. * Group 1: PQP hard tablet, 320 mg (N=12) * Group 2: PQP dispersible granule, 320 mg (N=12) Transition to Part 2: To minimize the risk to healthy participants, a decision on transitioning from Part 1 to Part 2, will be taken by the Safety Review Committee (SRC), based on the safety and preliminary PK interim report of the granule formulation, compared to the PQP hard tablet, with safety data obtained up to Day 15 and PK data obtained up to Day 8. If necessary, doses may be readjusted for the Part 2 to assess the food effect. Part 2: PQP dispersible granule administered in fed conditions (planned as 320 mg) * Group 3: High-fat meal (N=12) * Group 4: Low-fat meal representative of African diet (N=12) * Group 5: Whole milk 250 ml (N=12)

Study Record Dates

• First Submitted: June 26, 2023
• First Posted: July 5, 2023
• Study Start: August 14, 2023
• Primary Completion: December 6, 2023
• Study Completion: January 3, 2024
• Last Updated: March 18, 2025
• Results First Posted: March 6, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available within 6 months after study completion.
• Access Criteria: Requestors will be required to sign a Data Access Agreement.

Locations

TA (1)