MalariaPhase 2NCT01524341
Efficacy, Safety, Tolerability and Pharmacokinetics of KAE609 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection
A Phase 2 study testing KAE609 in people with Malaria, run by Novartis Pharmaceuticals at 3 sites in Thailand.
Trial 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 Read more about this study
- Who is it for?
- Ages 20 to 60 years
- Conditions the study is for
- Malaria
- What is being tested?
- KAE609
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 3 sitesThailand
- Study dates
- Jan 2012to Jun 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 20 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
Thailand3 sites
Novartis Investigative Site
Bangkok, 10400
Novartis Investigative Site
Tak, 63110
Novartis Investigative Site
Tak Province, 63110
About this study
Official title: 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
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
- Conditions
- Malaria
- Being tested
- KAE609
- Keywords
- Acute malaria, KAE609
- Medical subject headings
- Malaria, Acute malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KAE609Drug
KAE609 was supplied as capsules for oral use.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 10 subjects with Plasmodium vivax malaria will receive 30 mg KAE609 once a day for three days Receives: Drug: KAE609 |
| Cohort 2 | Experimental | 10 subjects with Plasmodium falciparum malaria will receive 30 mg KAE609 once a day for three days Receives: Drug: KAE609 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parasite clearance time
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.
Measured: From baseline to the time point when the blood parasite count is zero(up to a maximum of 5 days)
Secondary outcomes (8)
Number of participants with adverse events
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.
Measured: vital signs: Days 1 through 6; ECG: Days1, 2, 3; Labs: Days 2, 3, 5, study completion
Area under the curve (AUC)0-24h on 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
Measured: Day 1 and Day 3
The accumulation ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1)
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
Measured: Day 1 and Day 3
Maximum concentration (Cmax) on 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
Measured: Day 1 and Day 3
Time to maximum concentration (Tmax) on 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
Measured: Day 1 and Day 3
Half-life (T1/2)
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
Measured: Day 3
Clearance (CL/F )
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
Measured: Day 3
The apparent volume of distribution during the terminal elimination phase following extravascular administration (Vz/F)
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
Measured: Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2012 (estimated)
- Study startJan 2012
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01524341
- Sponsor's protocol ID
- CKAE609X2201
- Status last verified
- May 2013
- First submitted
- 30 Jan 2012
- Last updated
- 13 May 2013
- Results posted
- No
Publications
White NJ, Pukrittayakamee S, Phyo AP, Rueangweerayut R, Nosten F, Jittamala P, Jeeyapant A, Jain JP, Lefevre 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.
PubMed 25075833
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01524341
- Acronym / sponsor ID
- CKAE609X2201
- Conditions
- Malaria
- Keywords
- Acute malaria, KAE609
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 1 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: KAE60910 subjects with Plasmodium vivax malaria will receive 30 mg KAE609 once a day for three days |
| Cohort 2 | Experimental | Drug: KAE60910 subjects with Plasmodium falciparum malaria will receive 30 mg KAE609 once a day for three days |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
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 |
|---|---|---|
| KAE609KAE609 was supplied as capsules for oral use. | Drug | Cohort 1, Cohort 2 |
Primary outcome
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.
8 secondary outcomes
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
Area under the curve (AUC)0-24h on Day 1 and Day 3
Time frame: Day 1 and Day 3
The accumulation ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1)
Time frame: Day 1 and Day 3
Maximum concentration (Cmax) on Day 1 and Day 3
Time frame: Day 1 and Day 3
Time to maximum concentration (Tmax) on Day 1 and Day 3
Time frame: Day 1 and Day 3
Half-life (T1/2)
Time frame: Day 3
Clearance (CL/F )
Time frame: Day 3
The apparent volume of distribution during the terminal elimination phase following extravascular administration (Vz/F)
Time frame: Day 3
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2013.
- Derived from this study: PubMed 25075833White NJ, Pukrittayakamee S, Phyo AP, Rueangweerayut R, Nosten F, Jittamala P, Jeeyapant A, Jain JP, Lefevre 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.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KAE609 in people with Malaria, run by Novartis Pharmaceuticals at 3 sites in Thailand.
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 3 inclusion and 6 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 13 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Thailand. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01524341, which also lists 1 linked publication.
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 13 May 2013.