Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
To evaluate the potential effects of artemether- lumefantrine on the auditory function
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Artemether-lumefantrine (Coartem) | Experimental | Artemether-lumefantrine (Coartem) tablets containing 20 mg artemether and 120 mg lumefantrine twice a day for 3 days, dosage dependent on body weight. |
|
| Atovaquone-proguanil (Malarone) | Active Comparator | Atovaquone-proguanil (Malarone) tablets containing 250 mg atovaquone and 100 mg proguanil hydrochloride once daily for 3 days, dosage dependent on body weight. |
|
| Artesunate-mefloquine | Active Comparator | Artesunate-mefloquine tablets containing 50 mg artesunate (Plasmotrim) and 250 mg mefloquine (Mephaquin). Artesunate 4 mg/kg/day (for 3 days) and mefloquine 25 mg/kg/day (days 2 and 3) total dose was given once daily dependent upon body weight. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Artesunate-mefloquine | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Auditory Abnormalities at Day 7 Assessed by Auditory Brainstem Response (ABR) Wave III Latency Changes on Day 7(a Type of Hearing Test) | To demonstrate the safety of artemether-lumefantrine after 3 days of treatment in patients with acute, uncomplicated falciparum malaria by testing the null hypothesis that the rate of auditory abnormalities is ≥ 15% in the population treated with artemether-lumefantrine as assessed by ABR at Day 7 following initiation of treatment compared with their baseline values. An "auditory nerve abnormality" is here defined as a greater than 0.30 ms change in Wave III latency from baseline to Day 7. Exact Pearson-Clopper two-sided 95% confidence limits were constructed for all three treatment groups. | 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| Auditory Changes Following 3 Days of Treatment at Days 3, 7, 28, and 42 Days as Assessed by Pure Tone Thresholds Assessments (a Type of Hearing Test) | Audiometric measurements such as pure-tone threshold (air conduction tested at 250 to 8000 HZ) day 3, 7, 28 and 42 following initiation of treatment, including changes from baseline. Pure-tone average (PTA) calculated for each ear by averaging the pure-tone threshold values at 500, 1000, 2000 and 3000 HZ. |
Not provided
Inclusion Criteria
Exclusion Criteria
Other protocol-defined inclusion/exclusion criteria may apply.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Novartis | Novartis | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigational Site | Tumaco | Colombia |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Artemether-lumefantrine (Coartem) | Artemether-lumefantrine (Coartem) tablets containing 20 mg artemether and 120 mg lumefantrine twice a day for 3 days dosage dependent on body weight. |
| FG001 | Atovaquone-proguanil (Malarone) | Atovaquone-proguanil (Malarone) tablets containing 250 mg atovaquone and 100 mg proguanil hydrochloride once daily for 3 days dosage dependent on body weight. |
| FG002 | Artesunate-mefloquine | Artesunate (Plasmotrim) 50 mg tablet; based on body weight for a dosage of 4 mg/kg/day for 3 days- mefloquine (Mephaquin) 250 mg tablets; based on body weight for a total dosage of 25 mg/kg once daily on days 2 and 3. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Artemether-lumefantrine (Coartem) | Artemether-lumefantrine (Coartem) tablets containing 20 mg artemether and 120 mg lumefantrine twice a day for 3 days dosage dependent on body weight. |
| BG001 | Atovaquone-proguanil (Malarone) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Auditory Abnormalities at Day 7 Assessed by Auditory Brainstem Response (ABR) Wave III Latency Changes on Day 7(a Type of Hearing Test) | To demonstrate the safety of artemether-lumefantrine after 3 days of treatment in patients with acute, uncomplicated falciparum malaria by testing the null hypothesis that the rate of auditory abnormalities is ≥ 15% in the population treated with artemether-lumefantrine as assessed by ABR at Day 7 following initiation of treatment compared with their baseline values. An "auditory nerve abnormality" is here defined as a greater than 0.30 ms change in Wave III latency from baseline to Day 7. Exact Pearson-Clopper two-sided 95% confidence limits were constructed for all three treatment groups. | Safety per protocol set defined as all the randomized patients who took at least 80% of the entire recommended dose and had a valid baseline and Day 7 ABR Wave III latency evaluation and did not use any meds having an ototoxic effect. | Posted | Number | 95% Confidence Interval | Percentage of Participants | 7 days |
|
Not provided
Safety Set- All patients who received at least one dose of study drug and had at least one post baseline safety assessment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Artemether-lumefantrine | Artemether-lumefantrine |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
Not provided
| ID | Term |
|---|---|
| D008288 | Malaria |
| D016778 | Malaria, Falciparum |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D015767 | Mefloquine |
| C109496 | atovaquone, proguanil drug combination |
| D000077611 | Artemether, Lumefantrine Drug Combination |
| ID | Term |
|---|---|
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Atovaquone-proguanil |
| Drug |
|
|
| Artemether-lumefantrine | Drug |
|
|
| Baseline (Day 1), 3, 7, 28 and Day 42 |
| Relationship Between Changes in Auditory Function and Treatment Groups | ABR Wave III latency (ms) changes from baseline to Day 7 in the three drug exposure groups. | From Baseline to Day 7 |
| Efficacy of Polymerase Chain Reaction (PCR) Adjusted Malaria Cure Rates of the Three Treatment Regimens at Days 14, 28 and 42 | Percentage of patients with clearance of asexual parasitemia (observed by optical microscopy) within 7 days of initiation of trial treatment without recrudescence within 14, 28 and 42 days respectively after initiation of treatment. Patients with recurrent parasitemia and paired PCR results were classified as either a new infection (different paired genotypes) or a recrudescence (matching paired genotypes). Patients without paired PCR results or ambiguous results were classified as treatment failures. | Days 14, 28 and 42 |
Atovaquone-proguanil (Malarone) tablets containing 250 mg atovaquone and 100 mg proguanil hydrochloride once daily for 3 days dosage dependent on body weight.
| BG002 | Artesunate-mefloquine | Artesunate (Plasmotrim) 50 mg tablet; based on body weight for a dosage of 4 mg/kg/day for 3 days- mefloquine (Mephaquin) 250 mg tablets; based on body weight for a total dosage of 25 mg/kg once daily on days 2 and 3. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Body Weight | Mean | Standard Deviation | kg |
|
| OG000 | Artemether-lumefantrine (Coartem) | Artemether-lumefantrine (Coartem) tablets containing 20 mg artemether and 120 mg lumefantrine twice a day for 3 days dosage dependent on body weight. |
|
|
|
| Secondary | Auditory Changes Following 3 Days of Treatment at Days 3, 7, 28, and 42 Days as Assessed by Pure Tone Thresholds Assessments (a Type of Hearing Test) | Audiometric measurements such as pure-tone threshold (air conduction tested at 250 to 8000 HZ) day 3, 7, 28 and 42 following initiation of treatment, including changes from baseline. Pure-tone average (PTA) calculated for each ear by averaging the pure-tone threshold values at 500, 1000, 2000 and 3000 HZ. | Safety per protocol patients who had a valid ABR at baseline and on the specified day were included. | Posted | Mean | 95% Confidence Interval | dB | Baseline (Day 1), 3, 7, 28 and Day 42 |
|
|
|
| Secondary | Relationship Between Changes in Auditory Function and Treatment Groups | ABR Wave III latency (ms) changes from baseline to Day 7 in the three drug exposure groups. | Posted | Mean | 95% Confidence Interval | ms | From Baseline to Day 7 |
|
|
|
| Secondary | Efficacy of Polymerase Chain Reaction (PCR) Adjusted Malaria Cure Rates of the Three Treatment Regimens at Days 14, 28 and 42 | Percentage of patients with clearance of asexual parasitemia (observed by optical microscopy) within 7 days of initiation of trial treatment without recrudescence within 14, 28 and 42 days respectively after initiation of treatment. Patients with recurrent parasitemia and paired PCR results were classified as either a new infection (different paired genotypes) or a recrudescence (matching paired genotypes). Patients without paired PCR results or ambiguous results were classified as treatment failures. | Full Analysis Set defined as all randomized patients with confirmed malaria at baseline, who had at least one dose of study drug and had at least one relevant post-baseline efficacy assessment. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Days 14, 28 and 42 |
|
|
|
| 0 |
| 159 |
| 23 |
| 159 |
| EG001 | Atovaquone-proguanil | Atovaquone-proguanil | 0 | 53 | 17 | 53 |
| EG002 | Artesunate-Mefloquine | Artesunate-Mefloquine | 1 | 53 | 30 | 53 |
| Diarrhoea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| D000079426 |
| Vector Borne Diseases |
| D000077549 | Artemether |
| D037621 | Artemisinins |
| D017382 | Reactive Oxygen Species |
| D005609 | Free Radicals |
| D007287 | Inorganic Chemicals |
| D009930 | Organic Chemicals |
| D000078102 | Lumefantrine |
| D005449 | Fluorenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D012717 | Sesquiterpenes |
| D013729 | Terpenes |
| D011083 | Polycyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
|
| Change from baseline to Day 7 Right Ear |
|
| Change from baseline to Day 28 Right Ear |
|
| Change from baseline to Day 42 Right Ear |
|
| Baseline Left Ear |
|
| Change from baseline to Day 3 Left Ear |
|
| Change from baseline to Day 7 Left Ear |
|
| Change from baseline to Day 28 Left Ear |
|
| Change from baseline to Day 42 Left Ear |
|
|
| Baseline Left Ear |
|
| Change from baseline to Day 7 Left Ear |
|
|
| Day 42 |
|