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

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01103713
First received: April 7, 2010
Last updated: January 22, 2015
Last verified: January 2015
  Purpose

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.


Condition Intervention Phase
Asymptomatic Parasitemia In Pregnancy
Drug: Azithromycin plus chloroquine
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants With Parasitologic Response (Polymerase Chain Reaction (PCR) Corrected) at Day 28 Post First Dose of Study Medication [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 Post First Dose of Study Medication [ Time Frame: Days 7, 14, 21, 35, and 42 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 7, 14, 21, 35, and 42 ] [ Designated as safety issue: No ]
    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, 28, 35, and 42 Post First Dose of Study Medication [ Time Frame: Days 7, 14, 21, 28, 35, and 42 ] [ Designated as safety issue: No ]
    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 Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication [ Time Frame: Days 7, 14, 21, 28, 35, and 42 ] [ Designated as safety issue: No ]
    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.

  • Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication [ Time Frame: Days 7, 14, 21, 28, 35, and 42 ] [ Designated as safety issue: No ]
    Parasite counts (actual counts per microliter of blood) was measured at various time points.


Other Outcome Measures:
  • Summary of Pregnancy Outcome: Location of Delivery [ Time Frame: Following delivery or pregnancy termination ] [ Designated as safety issue: Yes ]
    All participants were followed up for exposure-in-utero (EIU) safety assessments following delivery or termination of pregnancy.

  • Summary of Pregnancy Outcome: Mode of Delivery [ Time Frame: Following delivery or pregnancy termination ] [ Designated as safety issue: Yes ]
    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? [ Time Frame: Following delivery or pregnancy termination ] [ Designated as safety issue: Yes ]
    All participants were followed up for EIU safety assessments following delivery or termination of pregnancy.

  • Summary of Pregnancy Outcome: Labor Induced? [ Time Frame: Following delivery or pregnancy termination ] [ Designated as safety issue: Yes ]
    All participants were followed up for EIU safety assessments following delivery or termination of pregnancy.

  • Summary of Pregnancy Outcome: Complications During Delivery? [ Time Frame: Following delivery or pregnancy termination ] [ Designated as safety issue: Yes ]
    All participants were followed up for EIU safety assessments following delivery or termination of pregnancy.

  • Summary of Pregnancy Outcome: Outcome of Birth [ Time Frame: Following delivery or pregnancy termination ] [ Designated as safety issue: Yes ]
    All participants were followed up for EIU safety assessments following delivery or termination of pregnancy.

  • Incidence of Fever Based on Oral Temperature [ Time Frame: Baseline, Days 1, 2, 7, 14, 21, 28, 35, and 42 ] [ Designated as safety issue: Yes ]
    Oral temp was taken by the fieldworker through Day 42.

  • Summary of Hemoglobin Concentration: Abnormal Hemoglobin Level [ Time Frame: Day 42 ] [ Designated as safety issue: Yes ]
    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 [ 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. ] [ Designated as safety issue: No ]
    AZ concentrations in the serum was determined at specified time points as PK endpoints

  • Summary of Plasma Chloroquine Concentration Versus Time [ 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. ] [ Designated as safety issue: No ]
    CQ concentrations in the plasma were determined at specified time points as PK endpoints

  • Summary of Plasma Desethylchloroquine Concentration Versus Time [ 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. ] [ Designated as safety issue: No ]
    CQ concentrations in the plasma were determined at specified time points as PK endpoints


Enrollment: 168
Study Start Date: March 2011
Study Completion Date: October 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Zithromax; Aralen

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.

  Eligibility

Ages Eligible for Study:   16 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01103713

Locations
Benin
Centre de Sante d'AHOUANSORI -AGUE
Cotonou, Benin
Hôpital Bethesda
Cotonou, Benin
Kenya
Siaya District Hospital
Siaya, Kenya
Malawi
Zomba Central Hospital
Zomba, Malawi
Tanzania
Teule Hospital
Muheza, Tanga, Tanzania
National Institute for Medical Research (Mwanza Centre)/ Nyamagana District Hospital
Mwanza, Tanzania, 1903
Uganda
Mulanda Health Centre IV
Kampala, Uganda
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01103713     History of Changes
Other Study ID Numbers: A0661201
Study First Received: April 7, 2010
Results First Received: July 16, 2014
Last Updated: January 22, 2015
Health Authority: Kenya: Ministry of Health
Tanzania: Food & Drug Administration

Keywords provided by Pfizer:
P. falciparum malaria
asymptomatic parasitemia
parasitological clearance
Intermittent Preventive Treatment of Falciparum Malaria in Pregnant Women (IPTp)

Additional relevant MeSH terms:
Parasitemia
Inflammation
Parasitic Diseases
Pathologic Processes
Sepsis
Systemic Inflammatory Response Syndrome
Chloroquine
Chloroquine diphosphate
Amebicides
Analgesics
Analgesics, Non-Narcotic
Anthelmintics
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antimalarials
Antinematodal Agents
Antiparasitic Agents
Antiprotozoal Agents
Antirheumatic Agents
Central Nervous System Agents
Filaricides
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015