Efficacy, Tolerability, PK of OZ439 in Adults With Acute, Uncomplicated P.Falciparum or Vivax Malaria Mono-infection

NCT01213966 | Completed Phase 2 Results DMC

• 1 other identifier: MMV_OZ439_10_002
• Study Type: interventional
• Target: 82
• Locations: 0 countries
• Sites: N/A

Brief Summary

A Phase IIa Exploratory, Open label, Single Dose Regimen, Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and Pharmacokinetics of OZ439 in adult patients with acute, uncomplicated Plasmodium falciparum or vivax malaria mono-infection.

Conditions

Malaria, Falciparum; Malaria, Vivax

Keywords

Acute uncomplicated Plasmodium Falciparum malaria; Blood stage Plasmodium Vivax malaria

Outcome Measures

Primary Outcomes (1)

• Derived Parasite Reduction Rate at 24 Hours (PPR24)

  PRR24 is the log10 change in parasitemia over 24 hours estimated from a regression model fit separately for each patient. The relationship between parasite counts and time was analyzed by fitting a variable lag phase, then a linear decline to the natural log of parasite count versus time relationship. The slope of this log linear relationship is the primary end-point. The time points chosen for the regression are those that yield the highest degree of significance when assessing the regression when the number of time points are greater than or equal to 3. No extrapolation was performed.

  24 hours after study drug administration

Study Arms (4)

800 mg OZ439 po single dose

EXPERIMENTAL

800 mg OZ439 po single dose

Drug: OZ439

400 mg OZ439 p.o. single dose

EXPERIMENTAL

400 mg OZ439 p.o. single dose

Drug: OZ439

200mg OZ439 p.o. single dose

EXPERIMENTAL

200mg OZ439 p.o. single dose

Drug: OZ439

1200 mg OZ439 po single dose

EXPERIMENTAL

1200 mg OZ439 po single dose

Drug: OZ439

Interventions

OZ439 DRUG

po, single dose

Also known as: Artefenomel

1200 mg OZ439 po single dose; 200mg OZ439 p.o. single dose; 400 mg OZ439 p.o. single dose; 800 mg OZ439 po single dose

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female patients between the age of 18 and 60 years, inclusive
• Body weight between 40 kg and 90 kg inclusive
• Presence of mono-infection of P. falciparum or P. vivax confirmed by:
• Fever, as defined by axillary temperature ≥ 37.5°C or oral/rectal/tympanic temperature ≥ 38°C, or history of fever in the previous 24 hours (history of fever must be documented) and,
• Microscopically confirmed parasite infection, 5,000 to 50,000 asexual parasite count/µl of blood
• Written informed consent, in accordance with local practice, provided by patient. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations
• Ability to swallow oral medication
• Ability and willingness to participate and access the health facility
• Agree to minimum of 4 days hospitalisation for drug administration and pharmacokinetic sampling

You may not qualify if:

• Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organisation Criteria 2010 (Attachment 2)
• Mixed Plasmodium infection
• Presence of other serious or chronic clinical condition requiring hospitalisation.
• Severe malnutrition (defined as the weight-for-height being below -3 standard deviation or less than 70% of median of the NCHS/WHO normalised reference values).
• Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTc interval greater than or equal to 450 msec), respiratory (including active tuberculosis), history of jaundice, hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric, history of convulsions or other abnormality (including head trauma).
• Known history of hypersensitivity, allergic or adverse reactions to artemisinin containing compounds or mefloquine or drug in the national guidelines for P. vivax.
• Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab).
• Have received any antimalarial treatment in the preceding 14 days, as determined by history and screening test.
• Have received antibacterial with known antimalarial activity in the preceding 14 days.
• Have received an investigational drug within the past 4 weeks.
• Liver function tests (ASAT/ALAT levels) more than 2 x ULN
• Hb level below 10 g/dL.
• Bilirubin levels greater than 40 µmol/L.
• Serum creatinine levels more than 2 times the upper limit of normal range in absence of dehydration. In case of important dehydration the creatinine should be lower than 2X ULN after oral/parenteral rehydration.
• Female patients must be neither pregnant (as demonstrated by a negative serum pregnancy test) nor lactating, and must be willing to take measures not to become pregnant during the study period and safety follow-up period

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Mahidol University: collaborator

Related Publications (1)

• Phyo AP, Jittamala P, Nosten FH, Pukrittayakamee S, Imwong M, White NJ, Duparc S, Macintyre F, Baker M, Mohrle JJ. Antimalarial activity of artefenomel (OZ439), a novel synthetic antimalarial endoperoxide, in patients with Plasmodium falciparum and Plasmodium vivax malaria: an open-label phase 2 trial. Lancet Infect Dis. 2016 Jan;16(1):61-69. doi: 10.1016/S1473-3099(15)00320-5. Epub 2015 Oct 5.

  PMID: 26448141 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria, Vivax

Interventions

artefenomel

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Professor Sasithon Pukrittayakamee
• Organization: Faculty of Tropical Medicine

yon@tropmedres.ac

(662) 354-9400-19

Study Officials

• Sasithon Pukrittayakamee, MD

  Mahidol University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2010
• First Posted: October 4, 2010
• Study Start: October 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: December 3, 2014
• Results First Posted: November 18, 2014

Record last verified: 2014-11