MalariaPhase 1NCT01958619
Open Label Pharmacokinetic Study of OZ439 and Piperaquine on Administration of OZ439+TPGS Granules for Oral Suspension Alone or With Either Piperaquine Phosphate Tablets or Granules for Oral Solution in Healthy Volunteers
A Phase 1 study testing 1440mg PQP tablets, 960mg PQP tablets and 800mg OZ439 + TPGS in people with Malaria, run by Medicines for Malaria Venture at 1 site in United Kingdom.
Trial summary
A healthy volunteer study to characterise the exposure of the two study medications, following administration of OZ439 + TPGS granules with piperaquine phosphate granules (intended for children) and with piperaquine phosphate tablets (intended for adults). 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?
- 1440mg PQP tablets, 960mg PQP tablets and 800mg OZ439 + TPGS
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2013to Jan 2014
- 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 or female, any race aged 18-55 years at screening
- body mass index of 18-30kg/m2 inclusive; and a total body weight >50kg and up to 100kg at screening
- Females must have negative pregnancy test at screening, be non-lactating and of non-childbearing potential confirmed by:
- natural (spontaneous) post-menopausal defined as amenorrheic for 12 months without an alternative medical cause with a screening FSH level >25IU/L for post menopause
- irreversible surgical sterilisation by bilateral oophorectomy or bilateral salpingectomy but not tubal ligation (with or without hysterectomy) at least six months ago
- Must agree to use acceptable methods of contraception Males must use acceptable methods of contraception if the male subject's partner could become pregnant from the time of the first administration of treatment or study medication until 3 months following administration of the last dose of study medication
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- One of the following acceptable methods of contraception must be used:
- Condom \& occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository)
- Surgical sterilisation (vasectomy with documentation of azoospermia) and a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository)
- Female partner uses oral contraceptives (combination oestrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method (as above)
- Female partner uses medically prescribed topically-applied transdermal contraceptive patch and a barrier method (as above)
- Female partner has had documented tubal ligation (sterilization). In addition, a barrier method (as above) must be used
- Female partner has had documented placement of an intrauterine device or system and the use of a barrier method (as above)
- True abstinence: when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Abstinent subjects must agree use one of the above-mentioned contraceptive methods, if sexual relationships start during the study or up to 90 days after the last dose of study drug
- Subjects should not donate egg and sperm from the time of administration of study medication until 3 months after 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 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
- History of allergic reaction to artemisinin-based compounds, 4-aminoquinolines such as piperaquine or any other clinically relevant allergy to drugs or food
- 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
- 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
- History of post-antibiotic colitis
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- Electrocardiogram abnormalities in the 12-lead Electrocardiogram (at screening) and/or 24-hour Holter Electrocardiogram (at screening) which in the opinion of the Investigator is clinically relevant or will interfere with the ECG analysis
- History of clinically significant Electrocardiogram abnormalities, or any of the following abnormalities at screening or on admission:
- PR >200ms
- QRS complex >120ms
- QTcB or QTcF >450ms or shortened QTcB or QTcF less than 340ms 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
- Positive results in any of the serology tests for Hepatitis B Surface Antigen, anti Hepatitis core antibody, Hepatitis C antibodies, and HIV 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 of screening
- Mentally handicapped
- Participation in a drug trial within 90 days of drug administration
- Use of ANY prescription or over the counter medications, within 3 weeks of study medication administration, or vitamins or herbal supplements within 2 weeks of administration of the study drug, unless prior approval is granted. Intermittent use of paracetamol at doses of up to 2g/day is permitted
- Use of moderate/strong inhibitors and/or inducers of CYP450 in 4 weeks of drug administration (or at least 5 half-lives of the compound whichever is the longer)
- Veins unsuitable for intravenous puncture or cannulation on either arm (veins difficult to locate, access or puncture, or veins with a tendency to rupture during or after puncture)
- Transaminases, bilirubin, serum potassium outside normal range at screening or admission
- Haemoglobin < lower limit of normal at screening or admission
- Donation of >500mL blood in 90 days prior to drug administration
- Must be non-smoker for at least three months before screening. "Tobacco use" includes smoking and the use of snuff and chewing tobacco, and other nicotine containing products. May not use any non-nicotine containing smoking cessation aids, e.g. varenicline, for at least three months before screening
- Any consumption of grapefruit, Seville oranges, wild grapes, black mulberries, pomegranates as 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 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 Ltd.
Croydon, London, CR7 7YE
About this study
Official title: Open Label Pharmacokinetic Study of OZ439 and Piperaquine Following Administration of OZ439+TPGS Granules for Oral Suspension Alone or With Either Piperaquine Phosphate Tablets or Granules for Oral Solution in the Fasted State in Healthy Volunteers
A healthy volunteer study to characterise the exposure of the two study medications, following administration of OZ439 + TPGS granules with piperaquine phosphate granules (intended for children) and with piperaquine phosphate tablets (intended for adults). Ideally, to confirm the exposure demonstrated in an earlier bioavailability study.
Read the detailed description
A Phase 1 open label parallel group, four arm study conducted in healthy male and female subject aged 18 to 55 years of age. Subjects will receive either treatment A, B, C or D as described below:
- Treatment A: 1440 mg PQP tablets and 800 mg OZ439 + TPGS granules for oral suspension
- Treatment B: 960 mg PQP tablets and 800 mg OZ439 + TPGS granules for oral suspension
- Treatment C: 960 mg PQP granules for oral solution and 800 mg OZ439 + TPGS granules for oral suspension
- Treatment D: 800 mg OZ439 + TPGS granules for oral suspension
- Conditions
- Malaria
- Being tested
- 1440mg PQP tablets, 960mg PQP tablets, 800mg OZ439 + TPGS, 960mg PQP granules
- Keywords
- open label, healthy volunteers, pharmacokinetic, parallel group
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1440mg PQP tabletsDrug
Piperaquine phosphate tablets (1440mg)
960mg PQP tabletsDrug
Piperaquine phosphate tablets (960mg)
800mg OZ439 + TPGSDrug
OZ439 (800mg) + TPGS granules for oral suspension
960mg PQP granulesDrug
Piperaquine phosphate granules for oral solution (960mg)
| Study group | Role | What they receive |
|---|---|---|
| Treatment A: 1440mg PQP tablets & 800mg OZ439 + TPGS | Experimental | Piperaquine phosphate tablets (1440mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions. Receives: Drug: 1440mg PQP tablets; Drug: 800mg OZ439 + TPGS |
| Treatment B: 960mg PQP tablets & 800mg OZ439 + TPGS | Experimental | Piperaquine phosphate tablets (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions. Receives: Drug: 960mg PQP tablets; Drug: 800mg OZ439 + TPGS |
| Treatment C: 960mg PQP granules & 800mg OZ439 + TPGS | Experimental | Piperaquine phosphate granules for oral solution (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions. Receives: Drug: 800mg OZ439 + TPGS; Drug: 960mg PQP granules |
| Treatment D: 800mg OZ439 + TPGS | Experimental | OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions. Receives: Drug: 800mg OZ439 + TPGS |
What is being measured
The primary outcome is the main question the study is designed to answer.
OZ439 Cmax
OZ439 observed maximum drug plasma concentration
Measured: Days 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) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 43.
OZ439 AUC0-∞
OZ439 Area under plasma concentration time curve from time zero extrapolated to infinity.
Measured: Days 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) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 43.
Secondary outcomes (2)
Piperaquine Cmax
Piperaquine Observed maximum drug plasma concentration
Measured: Days 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) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 43.
Piperaquine AUC0-∞
Piperaquine Area under plasma concentration time curve from time zero extrapolated to infinity.
Measured: Days 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) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 43.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionJan 2014
- Study completionJan 2014
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
- 55 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
- NCT01958619
- Sponsor's protocol ID
- MMV_OZ439_13_004
- Other IDs
- 2013-003409-25
- Status last verified
- Apr 2015
- First submitted
- 7 Oct 2013
- Last updated
- 8 May 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 8 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Pharmacokinetic Study of OZ439 and Piperaquine Following Administration of OZ439+TPGS Granules for Oral Suspension Alone or With Either Piperaquine Phosphate Tablets or Granules for Oral Solution in the Fasted State in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01958619
- Acronym / sponsor ID
- MMV_OZ439_13_004
- Conditions
- Malaria
- Keywords
- open label, healthy volunteers, pharmacokinetic, parallel group
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Medicines for Malaria VentureUniversity, hospital or other
- Collaborators
- Richmond Pharmacology Limited
- Study start
- Oct 2013
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 9 Oct 2013 (estimated)
- Results
- Posted 21 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A healthy volunteer study to characterise the exposure of the two study medications, following administration of OZ439 + TPGS granules with piperaquine phosphate granules (intended for children) and with piperaquine phosphate tablets (intended for adults). Ideally, to confirm the exposure demonstrated in an earlier bioavailability study.
Detailed description
A Phase 1 open label parallel group, four arm study conducted in healthy male and female subject aged 18 to 55 years of age. Subjects will receive either treatment A, B, C or D as described below:
- Treatment A: 1440 mg PQP tablets and 800 mg OZ439 + TPGS granules for oral suspension
- Treatment B: 960 mg PQP tablets and 800 mg OZ439 + TPGS granules for oral suspension
- Treatment C: 960 mg PQP granules for oral solution and 800 mg OZ439 + TPGS granules for oral suspension
- Treatment D: 800 mg OZ439 + TPGS granules for oral suspension
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment A: 1440mg PQP tablets & 800mg OZ439 + TPGS | Experimental | Drug: 1440mg PQP tablets, Drug: 800mg OZ439 + TPGSPiperaquine phosphate tablets (1440mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions. |
| Treatment B: 960mg PQP tablets & 800mg OZ439 + TPGS | Experimental | Drug: 960mg PQP tablets, Drug: 800mg OZ439 + TPGSPiperaquine phosphate tablets (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions. |
| Treatment C: 960mg PQP granules & 800mg OZ439 + TPGS | Experimental | Drug: 800mg OZ439 + TPGS, Drug: 960mg PQP granulesPiperaquine phosphate granules for oral solution (960mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions. |
| Treatment D: 800mg OZ439 + TPGS | Experimental | Drug: 800mg OZ439 + TPGSOZ439 (800mg) + TPGS granules for oral suspension under fasted conditions. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- healthy, male or female, any race aged 18-55 years at screening
- body mass index of 18-30kg/m2 inclusive; and a total body weight >50kg and up to 100kg at screening
- Females must have negative pregnancy test at screening, be non-lactating and of non-childbearing potential confirmed by:
- Must agree to use acceptable methods of contraception Males must use acceptable methods of contraception if the male subject's partner could become pregnant from the time of the first administration of treatment or study medication until 3 months following administration of the last dose of study medication
- Condom \& occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository)
Key exclusion criteria (29 listed)
- Male subjects with 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
- History of allergic reaction to artemisinin-based compounds, 4-aminoquinolines such as piperaquine or any other clinically relevant allergy to drugs or food
- 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
- 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
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 |
|---|---|---|
| 1440mg PQP tabletsPiperaquine phosphate tablets (1440mg) | Drug | Treatment A: 1440mg PQP tablets & 800mg OZ439 + TPGS |
| 960mg PQP tabletsPiperaquine phosphate tablets (960mg) | Drug | Treatment B: 960mg PQP tablets & 800mg OZ439 + TPGS |
| 800mg OZ439 + TPGSOZ439 (800mg) + TPGS granules for oral suspension | Drug | Treatment A: 1440mg PQP tablets & 800mg OZ439 + TPGS, Treatment B: 960mg PQP tablets & 800mg OZ439 + TPGS, Treatment C: 960mg PQP granules & 800mg OZ439 + TPGS, Treatment D: 800mg OZ439 + TPGS |
| 960mg PQP granulesPiperaquine phosphate granules for oral solution (960mg) | Drug | Treatment C: 960mg PQP granules & 800mg OZ439 + TPGS |
Primary outcome
OZ439 Cmax
Time frame: Days 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) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 43.
OZ439 observed maximum drug plasma concentration
OZ439 AUC0-∞
Time frame: Days 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) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 43.
OZ439 Area under plasma concentration time curve from time zero extrapolated to infinity.
2 secondary outcomes
Piperaquine Cmax
Time frame: Days 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) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 43.
Piperaquine AUC0-∞
Time frame: Days 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) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 43.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 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 1440mg PQP tablets, 960mg PQP tablets and 800mg OZ439 + TPGS 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 16 inclusion and 29 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 8 May 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 21 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: Days 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) and 168 (Day 8) hours post-dose. Sampling will also be done on Day 11, 15, 29 and 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 8 May 2015.