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

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Novartis ( Novartis Pharmaceuticals )

ClinicalTrials.gov Identifier:

NCT01524341

First received: January 30, 2012

Last updated: May 9, 2013

Last verified: May 2013

History of Changes

Tracking Information

First Received Date ^ICMJE

January 30, 2012

Last Updated Date

May 9, 2013

Start Date ^ICMJE

January 2012

Primary Completion Date

June 2012 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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) ] [ Designated as safety issue: No ]

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

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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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

Safety and tolerability [ Time Frame: vital signs: Days 1 through 6; ECG: Days1, 2, 3; Labs: Days 2, 3, 5, study completion ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Condition ^ICMJE

Malaria

Intervention ^ICMJE

Drug: KAE609

KAE609 was supplied as capsules for oral use.

Study Arm (s)

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

Enrollment ^ICMJE

Completion Date

June 2012

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.

Gender

Both

Ages

20 Years to 60 Years

Accepts Healthy Volunteers

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

Responsible Party

Novartis ( Novartis Pharmaceuticals )

Study Sponsor ^ICMJE

Novartis Pharmaceuticals

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:

Novartis Pharmaceuticals

Information Provided By

Novartis

Verification Date

May 2013

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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