Asymptomatic Parasitemia In Pregnancy
Conditions
Keywords
P. falciparum malaria, asymptomatic parasitemia, parasitological clearance, Intermittent Preventive Treatment of Falciparum Malaria in Pregnant Women (IPTp)
Brief summary
The study will be conducted in asymptomatic pregnant women with P. falciparum parasitemia. The subjects will be given 3 day dosing regiment of the fixed-dose combination of Azithromycin and Chloroquine. Parasitological clearance rate with polymerase chain reaction data will be evaluated on Day 28 as primary endpoint.
Detailed description
After interim analysis of efficacy data by an External Data Monitoring Committee, this study was terminated. Investigators were notified on 22 Aug 2013. There were no safety concerns that led to this termination.
Interventions
Study drug is a fixed dose tablet of AZCQ containing 250 mg AZ and 155 mg CQ base. All subjects will be administered a 3 day course of AZCQ IPTp regimen: a single dose of 1000 mg AZ/620 mg CQ base (4 fixed dose combination tablets of AZCQ: 250mg/155mg) administered per os (PO, orally) once daily for 3 days (Days 0, 1, 2).
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Primigravidae and secundigravidae pregnant women at \>=14 and \<=30 weeks of gestational age (confirmed by ultrasound examination). * Evidence of asymptomatic parasitemia with Plasmodium falciparum monoinfection (confirmed by microscopy) with parasite counts in the range of 80 100,000/uL on thick blood smears. * Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative if a subject is \<18 years of age) has been informed of all pertinent aspects of the study and that all questions by the subject have been sufficiently answered. Assent will be obtained from subjects \<18 years of age. * Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Exclusion criteria
* Age \<16 years old or \>35 years old. * Multiple gestations (more than one fetus) as per the ultrasound results at screening. * Clinical symptoms of malaria. * Hemoglobin \<8 g/dL (measured at baseline). * Any condition requiring hospitalization or evidence of severe concomitant infection at time of presentation. * Use of antimalarial drugs in previous 4 weeks. * History of convulsions, hypertension, diabetes or any other chronic illness that may adversely affect fetal growth and viability. * Known allergy to the study drugs (AZ, CQ, and SP) or to any macrolides or sulphonamides. * Requirement to use medication during the study that might interfere with the evaluation of the study drug of AZ or CQ or is contra indicated during pregnancy per package inserts. * Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. * Evidence of current obstetric complications that may adversely impact the pregnancy and/or fetal outcomes, including presence of congenital anomalies, placenta previa or abruption. * Known severe sickle cell (SS) disease or sickle hemoglobin C (SC) anemia. * Known family history of prolonged QT syndrome, serious ventricular arrhythmia, or sudden cardiac death.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Parasitologic Response (Polymerase Chain Reaction (PCR) Corrected) at Day 28 Post First Dose of Study Medication | Day 28 | The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure. |
| Percentage of Participants With Parasitologic Response (PCR Corrected) at Day 28 Post First Dose of Study Medication | Day 28 | The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Days 7, 14, 21, 28, 35, and 42 | The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure. |
| Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 Post First Dose of Study Medication | Days 7, 14, 21, 35, and 42 | The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure. |
| Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Days 7, 14, 21, 28, 35, and 42 | Parasite counts (actual counts per microliter of blood) was measured at various time points. |
| Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Days 7, 14, 21, 28, 35, and 42 | The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR uncorrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR uncorrected) through the day of consideration, otherwise she is a parasitological failure. |
| Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 , Post First Dose of Study Medication | Days 7, 14, 21, 35, and 42 | The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Summary of Hemoglobin Concentration: Abnormal Hemoglobin Level | Day 42 | Abnormal hemoglobin level on Day 42 was measured. The hemoglobin levels were measured with HemoCueTM, via finger stick or peripheral blood collection. The reference range was 10-16g/dL. Any value \<0.8 times lower limit of normal was considered clinically significant. |
| Summary of Serum Azithromycin Concentration Versus Time | Planned time: 0 (Day 0), 48 (Day 2), 50 (Day 2), 56 (Day 2), 168 (Day 7), and 336 (Day 14) hours post the first dose. Note: Assuming hour not specified as 0 hours on Day 7 and Day 14 for planned time post first dose calculation. | AZ concentrations in the serum was determined at specified time points as PK endpoints |
| Summary of Pregnancy Outcome: Location of Delivery | Following delivery or pregnancy termination | All participants were followed up for exposure-in-utero (EIU) safety assessments following delivery or termination of pregnancy. |
| Summary of Plasma Desethylchloroquine Concentration Versus Time | Planned time: 0 (Day 0), 48 (Day 2), 50 (Day 2), 56 (Day 2), 168 (Day 7), 336 (Day 14), 504 (Day 21) and 672 (Day 28) post first dose. Note: Assuming hour not specified as 0 hours on Days 7, 14, 21 and 28 for planned time post first dose calculation. | CQ concentrations in the plasma were determined at specified time points as PK endpoints |
| Summary of Plasma Chloroquine Concentration Versus Time | Planned time: 0 (Day 0), 48 (Day 2), 50 (Day 2), 56 (Day 2), 168 (Day 7), 336 (Day 14), 504 (Day 21) and 672 (Day 28) post first dose. Note: Assuming hour not specified as 0 hours on Days 7, 14, 21 and 28 for planned time post first dose calculation. | CQ concentrations in the plasma were determined at specified time points as PK endpoints |
| Summary of Pregnancy Outcome: Mode of Delivery | Following delivery or pregnancy termination | All participants were followed up for EIU safety assessments following delivery or termination of pregnancy. |
| Summary of Pregnancy Outcome: Delivery Assisted by Trained Obstetric Personnel? | Following delivery or pregnancy termination | All participants were followed up for EIU safety assessments following delivery or termination of pregnancy. |
| Summary of Pregnancy Outcome: Labor Induced? | Following delivery or pregnancy termination | All participants were followed up for EIU safety assessments following delivery or termination of pregnancy. |
| Summary of Pregnancy Outcome: Complications During Delivery? | Following delivery or pregnancy termination | All participants were followed up for EIU safety assessments following delivery or termination of pregnancy. |
| Summary of Pregnancy Outcome: Outcome of Birth | Following delivery or pregnancy termination | All participants were followed up for EIU safety assessments following delivery or termination of pregnancy. |
| Incidence of Fever Based on Oral Temperature | Baseline, Days 1, 2, 7, 14, 21, 28, 35, and 42 | Oral temp was taken by the fieldworker through Day 42. |
Countries
Benin, Kenya, Malawi, Tanzania, Uganda
Participant flow
Recruitment details
Participants were enrolled at 5 active sites in 5 countries: Benin (site 1012), Kenya (site 1004), Malawi (site 1015), Tanzania (site 1008), and Uganda (site 1013). The enrollment of the first participant took place on 07 March 2011 and the last participant last visit was on 25 October 2013.
Pre-assignment details
A total of 404 participants were screened and 168 participants were assigned to study drug, enrolled and treated. Of the 168 participants, two participants were excluded from the pharmacokinetic (PK) analysis, modified intent-to-treat (MITT), intent-to-treat (ITT) and per protocol (PP) populations due to informed consent protocol deviations.
Participants by arm
| Arm | Count |
|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) Study drug AZCQ is a fixed dose combination tablet of AZ and CQ containing 250 mg AZ and 155 mg CQ base. The dosing regimen evaluated in this study consisted of four AZCQ tablets (a total of 1000 mg AZ/620 mg CQ base), given orally once daily for 3 days (Days 0, 1, 2). | 168 |
| Total | 168 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other | 1 |
| Overall Study | Study terminated by sponsor | 2 |
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | Azithromycin (AZ)/Chloroquine (CQ) |
|---|---|
| Age, Customized 16-17 years | 41 Participants |
| Age, Customized <16 years | 0 Participants |
| Age, Customized 18-25 years | 125 Participants |
| Age, Customized 26-30 years | 1 Participants |
| Age, Customized 31-35 years | 1 Participants |
| Age, Customized >35 years | 0 Participants |
| Sex: Female, Male Female | 168 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 157 | 92 / 168 |
| serious Total, serious adverse events | 9 / 157 | 0 / 168 |
Outcome results
Primary
Percentage of Participants With Parasitologic Response (PCR Corrected) at Day 28 Post First Dose of Study Medication
The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure.
Time frame: Day 28
Population: PP population was used. PP is a subset of MITT population who had received all 3 days of study medication. Two participants were excluded because they had protocol deviations regarding the informed consent process.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Day 28 Post First Dose of Study Medication | 99.35 Percentage of participants |
Primary
Percentage of Participants With Parasitologic Response (Polymerase Chain Reaction (PCR) Corrected) at Day 28 Post First Dose of Study Medication
The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure.
Time frame: Day 28
Population: MITT population was used. MITT is a subset of the ITT population who had Plasmodium falciparum monoinfection (confirmed by microscopy) parasite count in the range of 80-100,000/microlitre on their baseline blood smear. Two participants were excluded because they had protocol deviations regarding the informed consent process.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (Polymerase Chain Reaction (PCR) Corrected) at Day 28 Post First Dose of Study Medication | 99.35 Percentage of participants |
Secondary
Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication
Parasite counts (actual counts per microliter of blood) was measured at various time points.
Time frame: Days 7, 14, 21, 28, 35, and 42
Population: PP population was used. PP is a subset of MITT population who received all 3 days of study medication. Two participants were excluded because they had protocol deviations regarding the informed consent process.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 7 (n=153) | 0.00 Parasite count per microliter | Standard Error 0 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 14 (n=152) | 0.00 Parasite count per microliter | Standard Error 0 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 21 (n=154) | 0.00 Parasite count per microliter | Standard Error 0 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 28 (n=154) | 219.73 Parasite count per microliter | Standard Error 111.46 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 35 (n=154) | 562.57 Parasite count per microliter | Standard Error 249.94 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 42 (n=153) | 919.75 Parasite count per microliter | Standard Error 476.92 |
Secondary
Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication
Parasite counts (actual counts per microliter of blood) was measured at various time points.
Time frame: Days 7, 14, 21, 28, 35, and 42
Population: ITT population was used. ITT is defined as all participants who received at least one dose of study medication and had a baseline blood smear positive for Plasmodium falciparum monoinfection, asexual parasitemia. Two participants were excluded because they had protocol deviations regarding the informed consent process.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 7 (n=155) | 0.00 Parasite count per microliter | Standard Error 0 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 14 (n=154) | 0.00 Parasite count per microliter | Standard Error 0 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 21 (n=156) | 0.00 Parasite count per microliter | Standard Error 0 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 28 (n=156) | 216.91 Parasite count per microliter | Standard Error 110.04 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 35 (n=156) | 555.36 Parasite count per microliter | Standard Error 246.77 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 42 (n=155) | 907.88 Parasite count per microliter | Standard Error 470.82 |
Secondary
Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication
Parasite counts (actual counts per microliter of blood) was measured at various time points.
Time frame: Days 7, 14, 21, 28, 35, and 42
Population: MITT population was used. MITT is a subset of the ITT population who had Plasmodium falciparum monoinfection (confirmed by microscopy) parasite count in the range of 80-100,000/microlitre on their baseline blood smear. Two participants were excluded because they had protocol deviations regarding the informed consent process.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 7 (n=153) | 0.00 Parasite count per microliter | Standard Error 0 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 14 (n=152) | 0.00 Parasite count per microliter | Standard Error 0 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 21 (n=154) | 0.00 Parasite count per microliter | Standard Error 0 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 28 (n=154) | 219.73 Parasite count per microliter | Standard Error 111.46 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 35 (n=154) | 562.57 Parasite count per microliter | Standard Error 249.94 |
| Azithromycin (AZ)/Chloroquine (CQ) | Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 42 (n=153) | 919.75 Parasite count per microliter | Standard Error 476.92 |
Secondary
Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication
The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure.
Time frame: Days 7, 14, 21, 28, 35, and 42
Population: ITT population was used. ITT is defined as all participants who received at least one dose of study medication and who had a baseline blood smear positive for Plasmodium falciparum monoinfection, asexual parasitemia. Two participants were excluded because they had protocol deviations regarding the informed consent process.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 7 (n=158) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 14 (n=156) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 21 (n=156) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 28 (n=156) | 99.36 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 35 (n=150) | 96.69 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 42 (n=140) | 95.26 Percentage of participants |
Secondary
Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 , Post First Dose of Study Medication
The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure.
Time frame: Days 7, 14, 21, 35, and 42
Population: PP population was used. PP is a subset of MITT population who had received all 3 days of study medication. Two participants were excluded because they had protocol deviations regarding the informed consent process.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 , Post First Dose of Study Medication | Day 7 (n=156) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 , Post First Dose of Study Medication | Day 14 (n=154) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 , Post First Dose of Study Medication | Day 21 (n=154) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 , Post First Dose of Study Medication | Day 35 (n=148) | 96.65 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 , Post First Dose of Study Medication | Day 42 (n=138) | 95.19 Percentage of participants |
Secondary
Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 Post First Dose of Study Medication
The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure.
Time frame: Days 7, 14, 21, 35, and 42
Population: MITT population was used. MITT is a subset of the ITT population who had Plasmodium falciparum monoinfection (confirmed by microscopy) parasite count in the range of 80-100,000/microlitre on their baseline blood smear. Two participants were excluded because they had protocol deviations regarding the informed consent process.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 Post First Dose of Study Medication | Day 7 (n=156) | 100 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 Post First Dose of Study Medication | Day 14 (n=154) | 100 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 Post First Dose of Study Medication | Day 21 (n=154) | 100 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 Post First Dose of Study Medication | Day 35 (n=148) | 96.65 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 Post First Dose of Study Medication | Day 42 (n=138) | 95.19 Percentage of participants |
Secondary
Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication
The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR uncorrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR uncorrected) through the day of consideration, otherwise she is a parasitological failure.
Time frame: Days 7, 14, 21, 28, 35, and 42
Population: MITT population was used. MITT is a subset of the ITT population who had Plasmodium falciparum monoinfection (confirmed by microscopy) parasite count in the range of 80-100,000/microlitre on their baseline blood smear. Two participants were excluded because they had protocol deviations regarding the informed consent process.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 7 (n=156) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 14 (n=154) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 21 (n=154) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 28 (n=154) | 95.45 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 35 (n=154) | 87.66 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 42 (n=152) | 78.43 Percentage of participants |
Secondary
Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication
The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR uncorrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR uncorrected) through the day of consideration, otherwise she is a parasitological failure.
Time frame: Days 7, 14, 21, 28, 35, and 42
Population: PP population was used. PP is a subset of MITT population who received all 3 days of study medication. Two participants were excluded because they had protocol deviations regarding the informed consent process.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 7 (n=156) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 14 (n=154) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 21 (n=154) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 28 (n=154) | 95.45 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 35 (n=154) | 87.66 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 42 (n=152) | 78.43 Percentage of participants |
Secondary
Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication
The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR uncorrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR uncorrected) through the day of consideration, otherwise she is a parasitological failure.
Time frame: Days 7, 14, 21, 28, 35, and 42
Population: ITT population was used. ITT is defined as all participants who received at least one dose of study medication and had a baseline blood smear positive for Plasmodium falciparum monoinfection, asexual parasitemia. Two participants were excluded because they had protocol deviations regarding the informed consent process.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 28 (n=156) | 95.51 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 7 (n=158) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 14 (n=156) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 21 (n=156) | 100.00 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 35 (n=156) | 87.82 Percentage of participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Day 42 (n=154) | 78.71 Percentage of participants |
Other Pre-specified
Incidence of Fever Based on Oral Temperature
Oral temp was taken by the fieldworker through Day 42.
Time frame: Baseline, Days 1, 2, 7, 14, 21, 28, 35, and 42
Population: ITT is defined as all participants who received at least one dose of study medication and who had a baseline blood smear positive for Plasmodium falciparum monoinfection, asexual parasitemia. Two participants were excluded because they had protocol deviations regarding the informed consent process.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Incidence of Fever Based on Oral Temperature | Baseline (n=165) | 0 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Incidence of Fever Based on Oral Temperature | Day 1 (n=161) | 0 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Incidence of Fever Based on Oral Temperature | Day 2 (n=160) | 0 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Incidence of Fever Based on Oral Temperature | Day 7 (n=156) | 0 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Incidence of Fever Based on Oral Temperature | Day 14 (n=155) | 0 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Incidence of Fever Based on Oral Temperature | Day 21 (n=155) | 0 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Incidence of Fever Based on Oral Temperature | Day 28 (n=156) | 0 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Incidence of Fever Based on Oral Temperature | Day 35 (n=156) | 0 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Incidence of Fever Based on Oral Temperature | Day 42 (n=155) | 4 Participants |
Other Pre-specified
Summary of Hemoglobin Concentration: Abnormal Hemoglobin Level
Abnormal hemoglobin level on Day 42 was measured. The hemoglobin levels were measured with HemoCueTM, via finger stick or peripheral blood collection. The reference range was 10-16g/dL. Any value \<0.8 times lower limit of normal was considered clinically significant.
Time frame: Day 42
Population: The safety analysis set consists of participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Hemoglobin Concentration: Abnormal Hemoglobin Level | 1 Participants |
Other Pre-specified
Summary of Plasma Chloroquine Concentration Versus Time
CQ concentrations in the plasma were determined at specified time points as PK endpoints
Time frame: Planned time: 0 (Day 0), 48 (Day 2), 50 (Day 2), 56 (Day 2), 168 (Day 7), 336 (Day 14), 504 (Day 21) and 672 (Day 28) post first dose. Note: Assuming hour not specified as 0 hours on Days 7, 14, 21 and 28 for planned time post first dose calculation.
Population: Analyses population included all participants who received at least one dose of study medication and had at least one blood sample collected for PK analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Chloroquine Concentration Versus Time | Hour 48 (Day 2) (n=158) | 305.827 ng/ml | Standard Deviation 129.02771 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Chloroquine Concentration Versus Time | Hour 50 (Day 2) (n=147) | 621.134 ng/ml | Standard Deviation 329.92731 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Chloroquine Concentration Versus Time | Hour 0 (Day 0) (n=160) | NA ng/ml | — |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Chloroquine Concentration Versus Time | Hour 56 (Day 2) (n=159) | 640.679 ng/ml | Standard Deviation 297.97628 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Chloroquine Concentration Versus Time | Hour 168 (Day 7) (n=155) | 129.835 ng/ml | Standard Deviation 92.19161 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Chloroquine Concentration Versus Time | Hour 336 (Day 14) (n=154) | 43.119 ng/ml | Standard Deviation 44.97312 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Chloroquine Concentration Versus Time | Hour 504 (Day 21) (n=156) | 22.382 ng/ml | Standard Deviation 46.83029 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Chloroquine Concentration Versus Time | Hour 672 (Day 28) (n=156) | 12.721 ng/ml | Standard Deviation 29.0538 |
Other Pre-specified
Summary of Plasma Desethylchloroquine Concentration Versus Time
CQ concentrations in the plasma were determined at specified time points as PK endpoints
Time frame: Planned time: 0 (Day 0), 48 (Day 2), 50 (Day 2), 56 (Day 2), 168 (Day 7), 336 (Day 14), 504 (Day 21) and 672 (Day 28) post first dose. Note: Assuming hour not specified as 0 hours on Days 7, 14, 21 and 28 for planned time post first dose calculation.
Population: Analyses population included all participants who received at least one dose of study medication and had at least one blood sample collected for PK analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Desethylchloroquine Concentration Versus Time | Hour 0 (Day 0) (n=158) | NA ng/ml | — |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Desethylchloroquine Concentration Versus Time | Hour 48 (Day 2) (n=158) | 183.622 ng/ml | Standard Deviation 118.86488 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Desethylchloroquine Concentration Versus Time | Hour 50 (Day 2) (n=147) | 220.424 ng/ml | Standard Deviation 130.48349 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Desethylchloroquine Concentration Versus Time | Hour 56 (Day 2) (n=159) | 241.831 ng/ml | Standard Deviation 137.88581 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Desethylchloroquine Concentration Versus Time | Hour 168 (Day 7) (n=155) | 144.088 ng/ml | Standard Deviation 123.66303 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Desethylchloroquine Concentration Versus Time | Hour 336 (Day 14) (n=154) | 55.513 ng/ml | Standard Deviation 54.78967 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Desethylchloroquine Concentration Versus Time | Hour 504 (Day 21) (n=156) | 29.825 ng/ml | Standard Deviation 32.418 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Plasma Desethylchloroquine Concentration Versus Time | Hour 672 (Day 28) (n=156) | 19.439 ng/ml | Standard Deviation 19.52079 |
Other Pre-specified
Summary of Pregnancy Outcome: Complications During Delivery?
All participants were followed up for EIU safety assessments following delivery or termination of pregnancy.
Time frame: Following delivery or pregnancy termination
Population: The safety analysis set consists of participants who received at least one dose of study medication. Data was available for 159 participants only.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Complications During Delivery? | Yes | 42 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Complications During Delivery? | No | 117 Participants |
Other Pre-specified
Summary of Pregnancy Outcome: Delivery Assisted by Trained Obstetric Personnel?
All participants were followed up for EIU safety assessments following delivery or termination of pregnancy.
Time frame: Following delivery or pregnancy termination
Population: The safety analysis set consists of participants who received at least one dose of study medication. Data was available for 159 participants only.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Delivery Assisted by Trained Obstetric Personnel? | Yes | 132 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Delivery Assisted by Trained Obstetric Personnel? | No | 27 Participants |
Other Pre-specified
Summary of Pregnancy Outcome: Labor Induced?
All participants were followed up for EIU safety assessments following delivery or termination of pregnancy.
Time frame: Following delivery or pregnancy termination
Population: The safety analysis set consists of participants who received at least one dose of study medication. Data was available for 158 participants only.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Labor Induced? | Yes | 3 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Labor Induced? | No | 155 Participants |
Other Pre-specified
Summary of Pregnancy Outcome: Location of Delivery
All participants were followed up for exposure-in-utero (EIU) safety assessments following delivery or termination of pregnancy.
Time frame: Following delivery or pregnancy termination
Population: The safety analysis set consists of participants who received at least one dose of study medication. Data was available for 160 participants only.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Location of Delivery | Medical facility | 130 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Location of Delivery | Home | 27 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Location of Delivery | Other (Not specified) | 3 Participants |
Other Pre-specified
Summary of Pregnancy Outcome: Mode of Delivery
All participants were followed up for EIU safety assessments following delivery or termination of pregnancy.
Time frame: Following delivery or pregnancy termination
Population: The safety analysis set consists of participants who received at least one dose of study medication. Data was available for 160 participants only.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Mode of Delivery | Vaginal | 145 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Mode of Delivery | Cesarean section | 15 Participants |
Other Pre-specified
Summary of Pregnancy Outcome: Outcome of Birth
All participants were followed up for EIU safety assessments following delivery or termination of pregnancy.
Time frame: Following delivery or pregnancy termination
Population: The safety analysis set consists of participants who received at least one dose of study medication. Data was available for 160 participants only.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Outcome of Birth | Spontaneous abortion | 0 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Outcome of Birth | Induced/elective abortion | 0 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Outcome of Birth | Full term live birth | 151 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Outcome of Birth | Premature birth | 6 Participants |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Pregnancy Outcome: Outcome of Birth | Stillbirth | 3 Participants |
Other Pre-specified
Summary of Serum Azithromycin Concentration Versus Time
AZ concentrations in the serum was determined at specified time points as PK endpoints
Time frame: Planned time: 0 (Day 0), 48 (Day 2), 50 (Day 2), 56 (Day 2), 168 (Day 7), and 336 (Day 14) hours post the first dose. Note: Assuming hour not specified as 0 hours on Day 7 and Day 14 for planned time post first dose calculation.
Population: Analyses population included all participants who received at least one dose of study medication and had at least one blood sample collected for PK analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Serum Azithromycin Concentration Versus Time | Hour 0 (Day 0) (n=161) | NA ng/ml | — |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Serum Azithromycin Concentration Versus Time | Hour 48 (Day 2) (n=158) | 194.145 ng/ml | Standard Deviation 63.76829 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Serum Azithromycin Concentration Versus Time | Hour 50 (Day 2) (n=147) | 994.463 ng/ml | Standard Deviation 552.23738 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Serum Azithromycin Concentration Versus Time | Hour 56 (Day 2) (n=159) | 707.682 ng/ml | Standard Deviation 326.72379 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Serum Azithromycin Concentration Versus Time | Hour 168 (Day 7) (n=155) | 54.444 ng/ml | Standard Deviation 24.34615 |
| Azithromycin (AZ)/Chloroquine (CQ) | Summary of Serum Azithromycin Concentration Versus Time | Hour 336 (Day 14) (n=153) | 20.307 ng/ml | Standard Deviation 31.57879 |