Piperaquine Granule Formulation Relative Bioavailability and Food Effect Study in Healthy Volunteers.
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      Adult participants who give written informed consent will be screened within 45 days to
      determine their eligibility before entering the trial on Day -1. The trial will initially
      establish the pharmacokinetic (PK) profile and estimated drug exposure of a single oral dose
      of PQP in a dispersible granule formulation compared to the PQP hard tablet formulation in
      the fasted state (Part 1). In the second study part, and based on the PK results of Part 1,
      it is intended to administer the same dose level of 320 mg PQP dispersible granules
      concomitant with different fed conditions. However, if from Part 1 of the study it is shown
      that PQP dispersible granules formulation provides a significant improvement in Cmax values
      in the fasted state, this dose level may be adjusted for Part 2, in order to take into
      account a potential 3-fold increase in exposure which is the observed food effect when
      film-coated tablets (Eurartesim®) are administered with a high fat/high calorie meal. Such
      dose adjustment will be based on the safety and preliminary PK interim results of the granule
      formulation in the fasted state. The PQP dose selected in Part 2 (as dispersible granules
      formulation) will take into account a 3-fold factor increase in exposure when administered
      with food (see above) with such predicted exposure in the presence of food being not higher
      than after the administration of 960 mg PQP in tablet of Eurartesim® in adult subjects dosed
      in fasting conditions. Furthermore, sufficient data will be available to address key
      questions on both, safety and PK parameters to enable the review and recommendation by the
      SRC for the optimal dose of the granule formulation to be administered in Part 2.
    

Intervention name(s): Piperaquine Phosphate; Piperaquine Phosphate
Intervention type(s): Drug; Drug
Intervention description(s): PQP hard tablet 320 mg; single dose (320 mg) given orally with 240 ml of water; PQP dispersible granules 320 mg dose equivalent dispersed in 25 ml of water; single dose (320 mg) given orally
Intervention MeSH terms: Piperaquine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 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)
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Pharmacokinetics; Malaria prevention; Bioavailability; Malaria; Food effect; Oral granule formulation