Asymptomatic Parasitemia In Pregnancy Clinical Trial
Official title:
An Open Label, Non-comparative Study To Evaluate Parasitological Clearance Rates And Pharmacokinetics Of Azithromycin And Chloroquine Following Administration Of A Fixed Dose Combination Of Azithromycin And Chloroquine (Azcq) In Asymptomatic Pregnant Women With Plasmodium Falciparum Parasitemia In Sub-saharan Africa
| Verified date | January 2015 |
| Source | Pfizer |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | Kenya: Ministry of HealthTanzania: Food & Drug Administration |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 168 |
| Est. completion date | October 2013 |
| Est. primary completion date | June 2013 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 16 Years to 35 Years |
| Eligibility |
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. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Benin | Centre de Sante d'AHOUANSORI -AGUE | Cotonou | |
| Benin | Hôpital Bethesda | Cotonou | |
| Kenya | Siaya District Hospital | Siaya | |
| Malawi | Zomba Central Hospital | Zomba | |
| Tanzania | Teule Hospital | Muheza | Tanga |
| Tanzania | National Institute for Medical Research (Mwanza Centre)/ Nyamagana District Hospital | Mwanza | |
| Uganda | Mulanda Health Centre IV | Kampala |
| Lead Sponsor | Collaborator |
|---|---|
| Pfizer |
Benin, Kenya, Malawi, Tanzania, Uganda,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | 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. | Following delivery or pregnancy termination | Yes |
| Other | Summary of Pregnancy Outcome: Mode of Delivery | All participants were followed up for EIU safety assessments following delivery or termination of pregnancy. | Following delivery or pregnancy termination | Yes |
| Other | 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. | Following delivery or pregnancy termination | Yes |
| Other | Summary of Pregnancy Outcome: Labor Induced? | All participants were followed up for EIU safety assessments following delivery or termination of pregnancy. | Following delivery or pregnancy termination | Yes |
| Other | Summary of Pregnancy Outcome: Complications During Delivery? | All participants were followed up for EIU safety assessments following delivery or termination of pregnancy. | Following delivery or pregnancy termination | Yes |
| Other | Summary of Pregnancy Outcome: Outcome of Birth | All participants were followed up for EIU safety assessments following delivery or termination of pregnancy. | Following delivery or pregnancy termination | Yes |
| Other | Incidence of Fever Based on Oral Temperature | Oral temp was taken by the fieldworker through Day 42. | Baseline, Days 1, 2, 7, 14, 21, 28, 35, and 42 | Yes |
| Other | 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. | Day 42 | Yes |
| Other | Summary of Serum Azithromycin Concentration Versus Time | AZ concentrations in the serum was determined at specified time points as PK endpoints | 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. | No |
| Other | Summary of Plasma Chloroquine Concentration Versus Time | CQ concentrations in the plasma were determined at specified time points as PK endpoints | 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. | No |
| Other | Summary of Plasma Desethylchloroquine Concentration Versus Time | CQ concentrations in the plasma were determined at specified time points as PK endpoints | 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. | No |
| 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. | Day 28 | No |
| 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. | Day 28 | No |
| 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. | Days 7, 14, 21, 35, and 42 | No |
| 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. | Days 7, 14, 21, 35, and 42 | No |
| 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. | Days 7, 14, 21, 28, 35, and 42 | No |
| 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. | Days 7, 14, 21, 28, 35, and 42 | No |
| 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. | Days 7, 14, 21, 28, 35, and 42 | No |