A Three Day Trial of Azithromycin Plus Chloroquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria

Study Overview
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Brief Summary
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The treatment of symptomatic, uncomplicated malaria caused by P. falciparum in adults.

Official Title
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A Phase 2, Open Label, Non-Comparative Trial Of Azithromycin 2000 mg Plus Chloroquine 600 Mg Base Daily For Three Days For The Treatment Of Uncomplicated Plasmodium Falciparum Malaria

Conditions
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Falciparum Malaria

Intervention / Treatment
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* Drug: Azithromycin plus chloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females greater then or equal to the age of 18 with uncomplicated, symptomatic malaria as indicated by the presence of blood smears positive for P. falciparum asexual parasitemia between 1000-100,000 parasites/uL and documented fever greater then or equal to 38.5 C/101.3 F rectal or fever greater then or equal to 38 C/100.4 F oral or history of fever as reported by subject within the prior 24 hours. Exclusion Criteria: Subjects with severe or complicated malaria. Pregnant or breast feeding women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azithromycin plus chloroquine<br>Single Arm, Open label study | Drug: Azithromycin plus chloroquine<br>* dose of 2000 mg Azithromycin plus 600 mg chloroquine base<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Parasite Clearance at Day 28 | Parasite clearance was defined as the clearance of asexual Plasmodium falciparum (P falciparum) parasitemia (defined as three consecutive 0 parasite counts) within 7 days of initiation of treatment, without subsequent recrudescence up to Day 28. Failure to achieve clearance of asexual P falciparum parasitemia was defined as parasitemia not cleared within 7 days of initiation of treatment, or subsequent recrudescence (confirmed by molecular testing) by Day 28 after achieving clearance. Percentage of participants with clearance is reported. Here N (Number of participants analyzed) signify participants who were evaluable (parasitological per protocol) at Day 28. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Early Treatment Failures (ETF) | ETF was defined as a participant meeting any of these criteria: development of signs of severe malaria (impaired consciousness [for example, obtundation, unarousable coma, delirium, stupor], respiratory distress [respiratory rate greater than or equal to {>=} 30 breaths/minute], seizures, hypoglycemia [glucose less than or equal to {<=} 40 milligram/deciliter], gross hematuria, increase in parasitemia to greater than 100,000 parasites/microliter in 48 hours or later after the first treatment dose was administered) any day from Day 0 to 3 in the presence of P falciparum parasitemia; parasite count on Day 2 > Day 0 (baseline), irrespective of axillary or oral temperature; parasite count on Day 3 > 37.5 degrees Celsius (axillary temperature) and >38 degrees Celsius (oral temperature) and parasite count on Day 3 >=25 percent (%) of the first available parasite density on Day 0 (baseline). | Baseline up to Day 28 | 
| Percentage of Participants With Late Treatment Failures (LTF) | LTF included late clinical failure (LCF) and late parasitologic failure (LPF). LCF is defined as a participant meeting any of these criteria: development of signs or symptoms of severe malaria after Day 3 in the presence of P falciparum parasitemia, without previously meeting any of the criteria of ETF or presence of P falciparum parasitemia and fever or history of fever on any day from Day 4 to Day 28, without previously meeting any of the criteria of ETF. LPF is defined as presence of P falciparum parasitemia on any day from Day 7 to Day 28 and the absence of fever or history of fever without previously meeting any of the criteria of ETF or LCF. | Baseline up to Day 28 | 
| Percentage of Participants With Resistance to Treatment | Resistance is measured by clearance of asexual P falciparum parasitemia and categorized into 3 levels; resistance I (RI): clearance of asexual P. falciparum parasitemia before Day 7 followed by recurrence on or after Day 7, resistance II (RII): marked reduction (<=25% of baseline) of asexual P. falciparum parasitemia but no clearance prior to and up to Day 7, and resistance III (RIII): no marked reduction (>25% of baseline) of asexual P. falciparum parasitemia. Recurrence was defined as the reappearance of asexual P. falciparum parasitemia following a quiescent or latent period after the cessation of the primary attack. Percentage of participants with resistance as measured by RI, RII and RIII is reported. | Days 7, 14, 21, 28, 35, 42 | 
| Percentage of Participants With Clinical Cure | Clinical Cure is defined as resolution of the participant's fever and other symptoms attributed to P falciparum malaria (for example, abdominal pain, malaise, and headache). | Day 3, 7, 28, and 42 | 
| Percentage of Participants With Parasite Clearance at Day 7, 14, 21, 35, 42 | Parasite clearance was defined as the clearance of asexual Plasmodium falciparum (P falciparum) parasitemia (defined as three consecutive 0 parasite counts) within 7 days of initiation of treatment, without subsequent recrudescence up to Day 28. Failure to achieve clearance of asexual P falciparum parasitemia was defined as parasitemia not cleared within 7 days of initiation of treatment, or subsequent recrudescence (confirmed by molecular testing) by Day 28 after achieving clearance. Percentage of participants with clearance is reported. Here N (Number of participants analyzed) signify participants who were evaluable (parasitological per protocol) at Day 28. | Day 7, 14, 21, 35, 42 | 
| Percentage of Participants With Gametocyte Clearance | Gametocyte clearance was defined as clearance of P falciparum gametocytemia (defined as attainment of 3 consecutive 0 gametocyte counts) without subsequent recurrence through the day of consideration. Recurrence was defined as the reappearance of asexual P. falciparum gametocytemia after achieving clearance. Percentage of participants with gametocyte clearance were reported. | Day 7, 14, 21, 28, 35, 42 | 
| Fever Clearance Time | Fever clearance time (FCT) was defined as the time from baseline to the first of 2 consecutive time points with temperature less than (<) 37.5 degree Celsius (C) (axillary temperature) or <38 degree C (oral temperature). | Baseline up to Day 42 | 
| Parasite Clearance Time | Asexual P falciparum parasite clearance time was defined as the time from baseline to the first of the 3 consecutive 0 parasite counts. | Baseline up to Day 42 |