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

NCT01958619 | Completed Phase 1 Results

• 2 other identifiers: MMV_OZ439_13_0042013-003409-25
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief 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). Ideally, to confirm the exposure demonstrated in an earlier bioavailability study.

Conditions

Malaria

Keywords

open label; healthy volunteers; pharmacokinetic; parallel group

Outcome Measures

Primary Outcomes (2)

• OZ439 Cmax

  OZ439 observed maximum drug plasma concentration

  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.

  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

  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-∞

  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.

Study Arms (4)

Treatment A: 1440mg PQP tablets & 800mg OZ439 + TPGS

EXPERIMENTAL

Piperaquine phosphate tablets (1440mg) and OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.

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.

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.

Drug: 800mg OZ439 + TPGS; Drug: 960mg PQP granules

Treatment D: 800mg OZ439 + TPGS

EXPERIMENTAL

OZ439 (800mg) + TPGS granules for oral suspension under fasted conditions.

Drug: 800mg OZ439 + TPGS

Interventions

1440mg PQP tablets DRUG

Piperaquine phosphate tablets (1440mg)

Treatment A: 1440mg PQP tablets & 800mg OZ439 + TPGS

960mg PQP tablets DRUG

Piperaquine phosphate tablets (960mg)

Treatment B: 960mg PQP tablets & 800mg OZ439 + TPGS

800mg OZ439 + TPGS DRUG

OZ439 (800mg) + TPGS granules for oral suspension

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 granules DRUG

Piperaquine phosphate granules for oral solution (960mg)

Treatment C: 960mg PQP granules & 800mg OZ439 + TPGS

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

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

Study Sites (1)

Richmond Pharmacology Ltd.

Croydon, London, CR7 7YE, United Kingdom

Location

MeSH Terms

Conditions

Malaria

Interventions

artefenomel; tocophersolan

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr Thomas Rueckle PhD
• Organization: Medicines for Malaria Venture (MMV)

ruecklet@mmv.org

+41 22 799 4567

Study Officials

• Ulrike Lorch, MD FRCA FFPM

  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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2013
• First Posted: October 9, 2013
• Study Start: October 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: May 8, 2015
• Results First Posted: April 21, 2015

Record last verified: 2015-04

Locations

GB (1)