Efficacy, Safety, Tolerability and Pharmacokinetics of KAE609 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection

Tracking Information
First Submitted Date ICMJE	January 30, 2012
First Posted Date ICMJE	February 1, 2012
Last Update Posted Date	May 13, 2013
Study Start Date ICMJE	January 2012
Actual Primary Completion Date	June 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 30, 2012)	Parasite clearance time [ Time Frame: From baseline to the time point when the blood parasite count is zero(up to a maximum of 5 days) ]; Calculated based on parasite count in blood. In thin film, use actual WBCs/µl, of blood to calculate parasite density by using the following formula: parasites/µl= #parasites× actual WBC/#WBCs counted. In thick film, assume that there are 250 RBCs per HPF, RBC count from 8 HPF equal 2000 RBC, Use actual RBCs/µl blood to calculate parasite density by using the following formula: parasites/µl= # of parasites in 8HPF/2000)× actual RBC.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01524341 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: September 20, 2012)	Number of participants with adverse events [ Time Frame: vital signs: Days 1 through 6; ECG: Days1, 2, 3; Labs: Days 2, 3, 5, study completion ]Number of participants with adverse events determined by Vital sign(body temperature, blood pressure and pulse rate): pre dose, 4, 8, 12, 16, 20, 24 hours post dose on Day 1: then 6, 12, 18, 24 hours post dose on each day during domiciles period until at least two consecutive normal temperature readings are obtained, then it will measure daily until Day 6. ECG: 3-4 hours post dose on day1; pre dose, 3-4 hours post dose on Day 2; pre dose, 3-4 hours post dose on Day 3 and study completion. Lab evaluation: Day 2, Day3 and Day5, study completion.; Area under the curve (AUC)0-24h on Day 1 and Day 3 [ Time Frame: Day 1 and Day 3 ]The parent drug in plasma samples will be analyzed. On Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. *The 24h sampling of first post dose should be taken before the second dose. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose; The accumulation ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) [ Time Frame: Day 1 and Day 3 ]The parent drug in plasma samples will be analyzed. On Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. *The 24h sampling of first post dose should be taken before the second dose. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose; Maximum concentration (Cmax) on Day 1 and Day 3 [ Time Frame: Day 1 and Day 3 ]The parent drug in plasma samples will be analyzed. On Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. *The 24h sampling of first post dose should be taken before the second dose. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose; Time to maximum concentration (Tmax) on Day 1 and Day 3 [ Time Frame: Day 1 and Day 3 ]The parent drug in plasma samples will be analyzed. On Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. *The 24h sampling of first post dose should be taken before the second dose. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose; Half-life (T1/2) [ Time Frame: Day 3 ]The parent drug in plasma samples will be analyzed On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose; Clearance (CL/F ) [ Time Frame: Day 3 ]The parent drug in plasma samples will be analyzed On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose; The apparent volume of distribution during the terminal elimination phase following extravascular administration (Vz/F) [ Time Frame: Day 3 ]The parent drug in plasma samples will be analyzed. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Original Secondary Outcome Measures ICMJE; (submitted: January 30, 2012)	Safety and tolerability [ Time Frame: vital signs: Days 1 through 6; ECG: Days1, 2, 3; Labs: Days 2, 3, 5, study completion ]Determined by vital signs, ECG evaluations, laboratory evaluations and adverse events. Vital sign(body temperature, blood pressure and pulse rate): pre dose, 4, 8, 12, 16, 20, 24 hours post dose on Day 1: then 6, 12, 18, 24 hours post dose on each day during domiciles period until at least two consecutive normal temperature readings are obtained, then it will measure daily until Day 6. ECG: 3-4 hours post dose on day1; pre dose, 3-4 hours post dose on Day 2; pre dose, 3-4 hours post dose on Day 3 and study completion. Lab evaluation: Day 2, Day3 and Day5, study completion.; Area under the curve (AUC)0-24h on Day 1 and Day 3 [ Time Frame: Day 1 and Day 3 ]The parent drug in plasma samples will be analyzed. On Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. *The 24h sampling of first post dose should be taken before the second dose. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose; The accumulation ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) [ Time Frame: Day 1 and Day 3 ]The parent drug in plasma samples will be analyzed. On Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. *The 24h sampling of first post dose should be taken before the second dose. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose; Maximum concentration (Cmax) on Day 1 and Day 3 [ Time Frame: Day 1 and Day 3 ]The parent drug in plasma samples will be analyzed. On Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. *The 24h sampling of first post dose should be taken before the second dose. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose; Time to maximum concentration (Tmax) on Day 1 and Day 3 [ Time Frame: Day 1 and Day 3 ]The parent drug in plasma samples will be analyzed. On Day 1: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. *The 24h sampling of first post dose should be taken before the second dose. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose; Half-life (T1/2) [ Time Frame: Day 3 ]The parent drug in plasma samples will be analyzed On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose; Clearance (CL/F ) [ Time Frame: Day 3 ]The parent drug in plasma samples will be analyzed On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose; The apparent volume of distribution during the terminal elimination phase following extravascular administrationi(Vz/F) [ Time Frame: Day 3 ]The parent drug in plasma samples will be analyzed. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Efficacy, Safety, Tolerability and Pharmacokinetics of KAE609 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection
Official Title ICMJE	A Proof-of-concept, Open Label, 3-day Repeated Dose Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of KAE609 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection
Brief Summary	This study will assess efficacy, safety , tolerability and PK in uncomplicated adult malaria patients with P. vivax or P. falciparum infection after 3 day dosing with KAE609 at 30 mg/day
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Malaria
Intervention ICMJE	Drug: KAE609; KAE609 was supplied as capsules for oral use.
Study Arms	Experimental: Cohort 1 10 subjects with Plasmodium vivax malaria will receive 30 mg KAE609 once a day for three days Intervention: Drug: KAE609; Experimental: Cohort 2 10 subjects with Plasmodium falciparum malaria will receive 30 mg KAE609 once a day for three days Intervention: Drug: KAE609
Publications *	White NJ, Pukrittayakamee S, Phyo AP, Rueangweerayut R, Nosten F, Jittamala P, Jeeyapant A, Jain JP, Lefèvre G, Li R, Magnusson B, Diagana TT, Leong FJ. Spiroindolone KAE609 for falciparum and vivax malaria. N Engl J Med. 2014 Jul 31;371(5):403-10. doi: 10.1056/NEJMoa1315860.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: May 9, 2013)	27
Original Estimated Enrollment ICMJE; (submitted: January 30, 2012)	20
Actual Study Completion Date	June 2012
Actual Primary Completion Date	June 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Male and female patients aged 20 to 60 years; Presence of mono-infection of P. falciparum or P. vivax; Weight between 40 kg to 90 kg Exclusion Criteria: Patients with signs and symptoms of severe/complicated malaria; Mixed Plasmodium infection; Presence of other serious or chronic clinical condition requiring hospitalization.; Severe malnutrition; Significant chronic medical conditions which in the opinion of the investigator preclude enrollment into the study Other protocol-defined inclusion/exclusion criteria may apply.
Sex/Gender	Sexes Eligible for Study: All
Ages	20 Years to 60 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Thailand
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01524341
Other Study ID Numbers ICMJE	CKAE609X2201
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Novartis ( Novartis Pharmaceuticals )
Study Sponsor ICMJE	Novartis Pharmaceuticals
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account	Novartis
Verification Date	May 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP