Evaluate Parasitological Clearance Rates And Pharmacokinetics Of The Combination Of Azithromycin And Chloroquine In Asymptomatic Pregnant Women With Falciparum Parasitemia In Africa

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

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.

Study Overview

• Status: Terminated
• Conditions: Asymptomatic Parasitemia In Pregnancy
• Intervention / Treatment: Drug: Azithromycin plus chloroquine

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.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 3

Contacts and Locations

Study Locations

• Benin
  • Cotonou, Benin
    • Hôpital Bethesda
  • Cotonou, Benin
    • Centre de Sante d'AHOUANSORI -AGUE
• Kenya
  • Siaya, Kenya
    • Siaya District Hospital
• Malawi
  • Zomba, Malawi
    • Zomba Central Hospital
• Tanzania
  • Mwanza, Tanzania, 1903
    • National Institute for Medical Research (Mwanza Centre)/ Nyamagana District Hospital
  • Tanga
    • Muheza, Tanga, Tanzania
      • Teule Hospital
• Uganda
  • Kampala, Uganda
    • Mulanda Health Centre IV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 33 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZCQ; Azithromycin/Chloroquine	Drug: Azithromycin plus chloroquine; 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).; Other Names: Zithromax; Aralen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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.
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.
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.

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: April 7, 2010
• First Submitted That Met QC Criteria: April 13, 2010
• First Posted (Estimate): April 15, 2010

Study Record Updates

• Last Update Posted (Estimate): January 26, 2015
• Last Update Submitted That Met QC Criteria: January 22, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: P. falciparum malaria; asymptomatic parasitemia; parasitological clearance; Intermittent Preventive Treatment of Falciparum Malaria in Pregnant Women (IPTp)
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Parasitic Diseases; Parasitemia; Anti-Infective Agents; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Amebicides; Chloroquine; Azithromycin
• Other Study ID Numbers: A0661201