MalariaPhase 1NCT01853475
Healthy Volunteer Study of the Pharmacokinetics of Oral Piperaquine With OZ439 + TPGS Formulation in the Fasted State
A Phase 1 study testing PQP tablets 960mg, PQP tablets 1440mg and OZ439+TPGS 800mg in people with Malaria, run by Medicines for Malaria Venture at 1 site in United Kingdom.
Trial summary
Piperaquine tablets (coated) + OZ439 granules + TPGS granules will be co-administered in Phase IIb (adults). However, safety and PK data (for OZ439 plus piperaquine) were obtained using piperaquine tablets plus OZ439 as Powder in Bottle with milk. Piperaquine has not yet been administered together with TPGS. 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?
- PQP tablets 960mg, PQP tablets 1440mg and OZ439+TPGS 800mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2013to Jul 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy male/female of any race aged 18-55 years at screening
- Body Mass Index 18-30kg/m2; body weight >50kg but no more than 100kg at screening
- Females with negative pregnancy test at screening and admission, non-lactating and of non-child bearing potential confirmed
- Agree to use acceptable methods of contraception
- Should not donate egg and sperm from the time of administration of treatment or study medication until 3 months following dose of study medication
- Must be capable of understanding and complying with the requirements of the protocol and must have signed the informed consent form prior to undergoing any study-related procedures
Who cannot join
- Male subjects with a female partner(s) who is (are) pregnant or lactating from the time of the administration of study medication
- Has a clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion, e.g. gastrectomy, diarrhoea.
- History of allergic reactions to artemisinin-based compounds, 4-aminoquinolines such as piperaquine or any other clinically relevant allergy to drugs or food.
- Any clinically relevant history of cow's milk intolerance/allergy.
- Any clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations conducted at screening or on admission. Exception is PR, QTcB, QTcF, cardiac rhythm, liver function tests and haemoglobin that must be within the normal reference range at screening and on admission.
- History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal (excluding appendectomy and cholecystectomy), haematological, endocrinological, immunological, metabolic, neurological, oncological, psychiatric, urological or other disease, or current infection
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- History of post-antibiotic colitis
- Electrocardiogram abnormalities in the standard 12-lead (at screening) and/or 24-hour 5 lead Holter (at screening) which in the opinion of the Investigator is clinically relevant or will interfere with the analysis
- A history of clinically significant electrocardiogram abnormalities, or any of the following abnormalities at screening or admission:
- PR >200 msec
- QRS complex >120 msec
- QTcB or QTcF >450 msec or shortened QTcB or QTcF less than 340 msec for males and females or family history of long QT syndrome or sudden death
- Any degree of heart block (such as first, second or third degree atrioventricular block, incomplete, full or intermittent bundle branch block)
- Abnormal T wave morphology / prominent U waves
- Potassium levels out of the normal range at screening and prior to dosing
- Positive results in any of the serology tests for Hepatitis B Surface Antigen, anti Hepatitis core antibody, Hepatitis C antibodies, and Human Immunodeficiency Virus 1 and 2 antibodies
- Confirmed positive results from urine drug screen (amphetamines, benzodiazepines, cocaine, cannabinoids, opiates, barbiturates, and methadone) or from the alcohol breath test at screening and admission
- History or clinical evidence of alcohol abuse, or any recreational drug abuse within the 2 years prior to screening
- Mentally handicapped
- Participation in a drug trial within 90 days prior to drug administration
- Use of ANY prescription or over the counter medications, within 3 weeks of study drug administration, or vitamins or herbal supplements within 2 week of administration of the drug administration of study drug (or at least 5 half-lives of the compound whichever period is the longer), unless prior approval is granted by both the Investigator and Sponsor. Excluded from this list is intermittent use of paracetamol at up to 2g/day.
- Use moderate or strong inhibitors and/or inducers of cytochrome CYP450 within 4 weeks prior to the planned drug administration (or at least 5 half-lives of the compound whichever period is the longer)
- Subjects have veins unsuitable for intravenous puncture or cannulation on either arm (e.g. veins that are difficult to locate, access or puncture veins with a tendency to rupture during or after puncture)
- Blood liver function tests not in the normal range at screening and on admission
- Haemoglobin is less than the lower limit of the reference range at screening and on admission.
- Donation of more than 500mL blood within 90 days prior to drug administration
- Subjects must be non-smokers for at least 3 months prior to screening Note: "Tobacco use" includes smoking and the use of snuff and chewing tobacco, and other nicotine or nicotine containing products
- Any consumption of grapefruit, Seville oranges, wild grapes, black mulberries, pomegranates in the form of fruit juice, marmalade or as a raw fruit within 7 days prior to dosing of study drug and throughout the study. Any circumstances or conditions, which, in the opinion of the investigator may affect full participation in the trial or compliance with the protocol
- Legal incapacity or limited legal capacity at screening
- Vegetarians, vegans or any dietary restrictions conflicting with the study standardised menus
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Richmond Pharmacology Limited
Croyden, London, CR7 7YE
About this study
Official title: Open Label, Parallel Group Study to Investigate the Pharmacokinetics (PK) Following Oral Co-administration of Piperaquine Phosphate (PQP) Tablets With a Prototype OZ439 + TPGS Formulation in the Fasted State in Healthy Volunteers
Piperaquine tablets (coated) + OZ439 granules + TPGS granules will be co-administered in Phase IIb (adults). However, safety and PK data (for OZ439 plus piperaquine) were obtained using piperaquine tablets plus OZ439 as Powder in Bottle with milk. Piperaquine has not yet been administered together with TPGS. Co-administration of piperaquine plus OZ439 as Powder in Bottle (PIB) with milk results in an increase in OZ439 exposure (current estimate ~ 70% due to a small drug drug interaction).
This study investigates the exposure of piperaquine and OZ439 when co-administered as piperaquine phosphate tablets and OZ439 + TPGS prototype (a formulation close to that of Phase IIb, but not identical), in order to select the appropriate doses for Phase IIb. The reference treatment is piperaquine phosphate tablets + OZ439 Powder in Bottle + full fat milk
Read the detailed description
Objectives:
- To evaluate the piperaquine and OZ439 pharmacokinetics when administered as a combination of piperaquine phosphate tablets with OZ439 / TPGS formulation in the fasted state
- To evaluate the piperaquine and OZ439 pharmacokinetics of a reference free combination formulation: piperaquine phosphate tablets with OZ439 powder in bottle (PIB) given with full fat milk
- To determine safety and tolerability of OZ439 and piperaquine phosphate when co-administered.
- Conditions
- Malaria
- Being tested
- PQP tablets 960mg, PQP tablets 1440mg, OZ439+TPGS 800mg, OZ439 PIB 800mg
- Keywords
- pharmacokinetics, safety, tolerability, bioavailability
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PQP tablets 960mgDrug
Piperaquine phosphate tablets 960mg
PQP tablets 1440mgDrug
Piperaquine phosphate tablets 1440mg
OZ439+TPGS 800mgDrug
OZ439+TPGS prototype formulation 800mg
OZ439 PIB 800mgDrug
OZ439 Powder in Bottle Aqueous Solution 800mg
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Experimental | PQP tablets 1440mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted. Receives: Drug: PQP tablets 1440mg; Drug: OZ439+TPGS 800mg |
| Treatment B | Experimental | PQP tablets 960mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted. Receives: Drug: PQP tablets 960mg; Drug: OZ439+TPGS 800mg |
| Treatment C - Reference | Active comparator | PQP Tablets 1440 mg and OZ439 PIB 800mg + full fat cow's milk Receives: Drug: PQP tablets 1440mg; Drug: OZ439 PIB 800mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
OZ439 Cmax
OZ439 maximum concentration observed
Measured: Day 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours(Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5),168 (Day 8), Day 11, Day 15, Day 29 and Day 43
OZ439 AUC0-inf
Area under the OZ439 plasma concentration time curve from time zero to time infinity using observed values.
Measured: Day 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours(Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5),168 (Day 8), Day 11, Day 15, Day 29 and Day 43
Secondary outcomes (2)
Piperaquine Cmax
Piperaquine maximum concentration observed
Measured: Day 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours(Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5),168 (Day 8), Day 11, Day 15, Day 29 and Day 43
Piperaquine AUC0-inf
Area under the Piperaquine plasma concentration time curve from time zero to time infinity using observed values.
Measured: Day 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours(Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5),168 (Day 8), Day 11, Day 15, Day 29 and Day 43
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2013 (estimated)
- Study startApr 2013
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medicines for Malaria Venture
- Sponsor type
- University, hospital or other
- Collaborators
- Richmond Pharmacology Limited
- Responsible party
- Sponsor
- Investigators
- Ulrike Lorch, MD FRCA FFPM, Principal investigator, Richmond Pharmacology Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01853475
- Sponsor's protocol ID
- MMV_OZ439_13_002
- Other IDs
- 2013-000983-28
- Status last verified
- Apr 2015
- First submitted
- 10 May 2013
- Last updated
- 30 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label, Parallel Group Study to Investigate the Pharmacokinetics (PK) Following Oral Co-administration of Piperaquine Phosphate (PQP) Tablets With a Prototype OZ439 + TPGS Formulation in the Fasted State in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01853475
- Acronym / sponsor ID
- MMV_OZ439_13_002
- Conditions
- Malaria
- Keywords
- pharmacokinetics, safety, tolerability, bioavailability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Medicines for Malaria VentureUniversity, hospital or other
- Collaborators
- Richmond Pharmacology Limited
- Study start
- Apr 2013
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 15 May 2013 (estimated)
- Results
- Posted 8 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Piperaquine tablets (coated) + OZ439 granules + TPGS granules will be co-administered in Phase IIb (adults). However, safety and PK data (for OZ439 plus piperaquine) were obtained using piperaquine tablets plus OZ439 as Powder in Bottle with milk. Piperaquine has not yet been administered together with TPGS. Co-administration of piperaquine plus OZ439 as Powder in Bottle (PIB) with milk results in an increase in OZ439 exposure (current estimate ~ 70% due to a small drug drug interaction).
This study investigates the exposure of piperaquine and OZ439 when co-administered as piperaquine phosphate tablets and OZ439 + TPGS prototype (a formulation close to that of Phase IIb, but not identical), in order to select the appropriate doses for Phase IIb. The reference treatment is piperaquine phosphate tablets + OZ439 Powder in Bottle + full fat milk
Detailed description
Objectives:
- To evaluate the piperaquine and OZ439 pharmacokinetics when administered as a combination of piperaquine phosphate tablets with OZ439 / TPGS formulation in the fasted state
- To evaluate the piperaquine and OZ439 pharmacokinetics of a reference free combination formulation: piperaquine phosphate tablets with OZ439 powder in bottle (PIB) given with full fat milk
- To determine safety and tolerability of OZ439 and piperaquine phosphate when co-administered.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Experimental | Drug: PQP tablets 1440mg, Drug: OZ439+TPGS 800mgPQP tablets 1440mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted. |
| Treatment B | Experimental | Drug: PQP tablets 960mg, Drug: OZ439+TPGS 800mgPQP tablets 960mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted. |
| Treatment C - Reference | Active comparator | Drug: PQP tablets 1440mg, Drug: OZ439 PIB 800mgPQP Tablets 1440 mg and OZ439 PIB 800mg + full fat cow's milk |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Healthy male/female of any race aged 18-55 years at screening
- Body Mass Index 18-30kg/m2; body weight >50kg but no more than 100kg at screening
- Females with negative pregnancy test at screening and admission, non-lactating and of non-child bearing potential confirmed
- Agree to use acceptable methods of contraception
- Should not donate egg and sperm from the time of administration of treatment or study medication until 3 months following dose of study medication
Key exclusion criteria (30 listed)
- Male subjects with a female partner(s) who is (are) pregnant or lactating from the time of the administration of study medication
- Has a clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion, e.g. gastrectomy, diarrhoea.
- History of allergic reactions to artemisinin-based compounds, 4-aminoquinolines such as piperaquine or any other clinically relevant allergy to drugs or food.
- Any clinically relevant history of cow's milk intolerance/allergy.
- Any clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations conducted at screening or on admission. Exception is PR, QTcB, QTcF, cardiac rhythm, liver function tests and haemoglobin that must be within the normal reference range at screening and on admission.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PQP tablets 960mgPiperaquine phosphate tablets 960mg | Drug | Treatment B |
| PQP tablets 1440mgPiperaquine phosphate tablets 1440mg | Drug | Treatment A, Treatment C - Reference |
| OZ439+TPGS 800mgOZ439+TPGS prototype formulation 800mg | Drug | Treatment A, Treatment B |
| OZ439 PIB 800mgOZ439 Powder in Bottle Aqueous Solution 800mg | Drug | Treatment C - Reference |
Primary outcome
OZ439 Cmax
Time frame: Day 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours(Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5),168 (Day 8), Day 11, Day 15, Day 29 and Day 43
OZ439 maximum concentration observed
OZ439 AUC0-inf
Time frame: Day 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours(Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5),168 (Day 8), Day 11, Day 15, Day 29 and Day 43
Area under the OZ439 plasma concentration time curve from time zero to time infinity using observed values.
2 secondary outcomes
Piperaquine Cmax
Time frame: Day 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours(Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5),168 (Day 8), Day 11, Day 15, Day 29 and Day 43
Piperaquine AUC0-inf
Time frame: Day 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours(Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5),168 (Day 8), Day 11, Day 15, Day 29 and Day 43
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ulrike Lorch, MD FRCA FFPM principal investigator
Richmond Pharmacology Limited
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PQP tablets 960mg, PQP tablets 1440mg and OZ439+TPGS 800mg in people with Malaria, run by Medicines for Malaria Venture 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 6 inclusion and 30 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 30 Apr 2015. 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?
Yes. Results are posted in the registry (first posted 8 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
OZ439 Cmax (time frame: Day 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours(Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5),168 (Day 8), Day 11, Day 15, Day 29 and Day 43). The study lists 2 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 30 Apr 2015.