A Healthy Volunteer Safety Study of Pyronaridine Tetraphosphate Taken in Combination With Piperaquine Tetraphosphate

NCT05160363 | Completed Phase 1 Results

• 1 other identifier: MMV_SMC_21_01
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a clinical trial involving two medicines called piperaquine (PQP) and pyronaridine (PYR) which, in combination with dihydroartemisinin (DHA) and with artesunate (ART) respectively, have been in clinical use for over 20 years to treat acute episodes of malaria. PYR and PQP are both known to be well tolerated and provide effective treatment for malarial infection when administered in their licensed combinations, but have not been administered together in combination before. This new combination is being considered for development for malaria prevention (i.e. chemoprophylaxis) in sub-Saharan Africa and therefore, the trial participants will be exclusively drawn from a population from that origin.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• The Incidence, Severity and Relationship of Treatment-Emergent Adverse Events (TEAEs).

  From start of IP administration - to follow up visit, Day 30

Study Arms (4)

PYR and PQP Combination

EXPERIMENTAL

Single dose in the morning on Days 1, 2 and 3 of the study Pyronaridine tetraphosphate 540 mg (three tablets) if body weight 50kg - \<65kg; OR, 720 mg (4 tablets) if body weight is ≥65 kg Piperaquine tetraphosphate 960 mg (three tablets) if body weight 50kg - \<75kg; OR, 1280 mg (4 tablets) if body weight ≥75kg

Drug: Pyronaridine Tetraphosphate; Drug: Piperaquine tetraphosphate

PYR and Placebo Combination

PLACEBO COMPARATOR

Single dose in the morning on Days 1, 2 and 3 of the study Pyronaridine tetraphosphate 540 mg (three tablets) if body weight 50kg - \<65kg; OR, 720 mg (4 tablets) if body weight is ≥65 kg Matched placebo for piperaquine (3 or 4 tablets based on body weight)

Drug: Pyronaridine Tetraphosphate; Drug: Placebo

PQP and Placebo Combination

PLACEBO COMPARATOR

Single dose in the morning on Days 1, 2 and 3 of the study Piperaquine tetraphosphate 960 mg (three tablets) if body weight 50kg - \<75kg; OR, 1280 mg (4 tablets) if body weight ≥75kg Matched placebo for pyronaridine (3 or 4 tablets based on body weight)

Drug: Piperaquine tetraphosphate; Drug: Placebo

Placebo Combination

SHAM COMPARATOR

Single dose in the morning on Days 1, 2 and 3 of the study Matched placebo for pyronaridine (3 or 4 tablets dependent on body weight) and matched placebo piperaquine (3 or 4 tablets dependent on body weight)

Drug: Placebo

Interventions

Pyronaridine Tetraphosphate DRUG

A total of 24 participants will be dosed with pyronaridine tetraphosphate, sixteen participants will be additionally be dosed with piperaquine tetraphosphate, eight patients will additionally be dosed with placebo.

PYR and PQP Combination; PYR and Placebo Combination

Piperaquine tetraphosphate DRUG

A total of 24 participants will be dosed with piperaquine tetraphosphate, sixteen participants will be additionally be dosed with pyronaridine tetraphosphate, eight patients will additionally be dosed with placebo.

PQP and Placebo Combination; PYR and PQP Combination

Placebo DRUG

Placebo tablets will be administered in combination with pyronaridine tetraphosphate (8 patients), OR, in combination with piperaquine tetraphosphate (8 patients), OR, only matched placebo tablets will be administered (8 patients)

PQP and Placebo Combination; PYR and Placebo Combination; Placebo Combination

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy as defined by:
• the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, haematological, immunological, psychiatric, gastrointestinal, renal, hepatic and metabolic disease
• Participants must agree to use the following contraceptive requirements for the applicable duration:
• Female participants of non-childbearing potential (WNCBP): Defined as either postmenopausal (evidence of menopause based on a combination of amenorrhea for at least one year and increased serum follicle-stimulating hormone (FSH) level \[\>30 IU/L\]), or surgical sterilisation (evidence of hysterectomy and/or bilateral oophorectomy) CONTRACEPTION REQUIRED: None
• Female participants of childbearing potential (WOCBP) who anticipate being sexually active with a male during the trial (from one complete menstrual cycle prior to the first IMP administration until 13 weeks after the last IMP administration):
• CONTRACEPTION REQUIRED: Highly effective contraception must start one complete menstrual cycle prior to the first day of dosing and continue until 13 weeks after the last IMP administration. Highly effective contraception methods for WOCBP include:
• combined (i.e. oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation:
• oral
• intravaginal
• transdermal
• progestogen-only hormonal contraception associated with inhibition of ovulation:
• oral
• injectable
• implantable
• intrauterine hormone-releasing system (IUS)

You may not qualify if:

• Current or recurrent disease (e.g. cardiovascular, haematological, neurological, endocrine, immunological, renal, hepatic or gastrointestinal or other conditions, including cholecystectomy or gastrectomy) that could affect the action, absorption, distribution, metabolism or excretion of PYR or PQP or could affect clinical assessments or clinical laboratory evaluations
• Any history of seizures or epilepsy
• Any history of photosensitivity
• Any documented retinopathy
• History of malaria in the previous two years
• A score of 20 or more on the Beck Depression Inventory, and/or a response of 1, 2 or 3 for item 9 of this inventory (related to suicidal ideation) \[26\].
• Current or relevant history of physical or psychiatric illness that are not stable or may require a change in treatment, or use of prohibited therapies during the trial, that make the participant unlikely to fully comply with the requirements of the trial or to complete the trial, or any condition that presents undue risk from the investigational product or trial procedures
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or may influence the result of the trial or the participant's ability to participate in the trial
• The history or presence of any of the following cardiac conditions: known structural cardiac abnormalities; family history of long QT syndrome; cardiac syncope or recurrent, idiopathic syncope; exercise-related clinically significant cardiac events
• Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG or clinically important abnormalities that may interfere with the interpretation of QTc interval changes. This includes participants with any of the following (at screening or Day -1):
• sinus node dysfunction
• clinically significant PR \>220 msecs (PQ) interval prolongation
• second- or third-degree atrioventricular (AV) block
• sustained cardiac arrhythmia's including (but not limited to) atrial fibrillation or supraventricular tachycardia, or any symptomatic arrhythmia, with the exception of isolated extra-systoles
• abnormal T-wave morphology which may impact on the QT/QTc assessment

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Richmond Pharmacology Limited: collaborator
• PharmaKinetic Ltd: collaborator

Study Sites (1)

Richmond Pharmacology Ltd

London, SE1 1YR, United Kingdom

Location

Related Publications (1)

• Felices M, Borghini-Fuhrer I, Abla N, Chalon S. Concentration-Response Analysis of the Combination of Pyronaridine and Piperaquine on Corrected QT Interval From a Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults of African Sub-Saharan Origin. Clin Transl Sci. 2025 Jul;18(7):e70305. doi: 10.1111/cts.70305.

  PMID: 40689586 DERIVED

MeSH Terms

Interventions

pyronaridine; piperaquine

Results Point of Contact

• Title: Senior Director, Program Leadership and Strategy
• Organization: Medicines for Malaria

borghinii@mmv.org

+41 22 555 03 26

Study Officials

• Stephan Chalon, MD PhD

  MMV Medicines for Malaria Venture

  STUDY DIRECTOR

• Ulrike Lorch, MD

  Richmond Pharmacology Limited

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2021
• First Posted: December 16, 2021
• Study Start: February 14, 2022
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: May 10, 2024
• Results First Posted: May 10, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)