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A Safety, Tolerability, Pharmacokinetic and Efficacy Study of Azithromycin Plus Piperaquine as Presumptive Treatment in Pregnant PNG Women

Primary Purpose

Pregnancy, Infections, Plasmodia, Drug Kinetics

Status

Unknown status

Phase

Phase 4

Locations

Papua New Guinea

Study Type

Interventional

Intervention

Azithromycin plus piperaquine phosphate

Sulfadoxine-pyrimethamine

About this trial

This is an interventional prevention trial for Pregnancy focused on measuring Azithromycin, Piperaquine, IPTp, Pharmacokinetics, Efficacy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

>14 weeks and <30 weeks gestation
No signs of severe malaria by World Health Organisation criteria
No significant concomitant disease (such as TB)
No prior history of an adverse reaction to AZI or PQP
No prior treatment with these drugs in the past 4 weeks
Can attend all follow-up visits
Provide informed consent

Exclusion Criteria:

Have signs of severe malaria by WHO criteria
Significant concomitant disease such as TB as assessed by the attending clinician
A history/family history of sudden death or of congenital prolongation of the QTc interval
Any clinical condition known to prolong the QTc interval
A history of complicated pregnancies/deliveries
A prior history of an adverse reaction to AZI or PQP
Have taken these drugs in the past 4 weeks
Cannot attend any of the follow-up visits
Do not provide informed consent

Sites / Locations

Papua New Guinea Institute of Medical ResearchRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Efficacy Study: Azithromycin plus piperaquine

Efficacy Study Control: National Standard Treatment

Pharmacokinetic Study: Azithromycin plus piperaquine

Arm Description

At baseline, participants receive three daily doses (0, 24 and 48 hours) of i) 1 g azithromycin as 2 x film-coated 500 mg tablets ii) 960 mg piperaquine tetraphosphate tablets as 3 x 320 mg tablets

At baseline, participants receive a single dose of sulfadoxine-pyrimethamine comprising 1,500 mg of sulfadoxine and 75 mg pyrimethamine in tablet form

At baseline, participants receive three daily doses (0, 24 and 48 hours) of i) 1 g azithromycin as 2 x film-coated 500 mg tablets ii) 960 mg piperaquine tetraphosphate tablets as 3 x 320 mg tablets

Outcomes

Primary Outcome Measures

Efficacy of azithromycin plus piperaquine for the prevention of malaria during pregnancy

The efficacy of azithromycin plus piperaquine for the prevention of malaria infection during pregnancy will be investigated in 120 women. Women will be randomized to receive either (i) 3 daily doses of AZI plus PQ, or, (ii) single dose sulfadoxine-pyrimethamine Participants will be actively followed for a period of 42 days (1, 2, 3, 4, 7, 14, 21, 28 and 42 days after treatment). At each follow-up time point the participant will have a clinical examination, fundal height measurement and assessment of foetal lie, perform a symptoms questionnaire, blood film for malaria and other scheduled safety tests (eg. Hb, glucose, ultrasound). A single blood sample for pharmacokinetic analysis will be collected at Day 4. At delivery all participants and their babies will be assessed, including blood sample for Hb, glucose, blood spot for PCR, cord blood and maternal blood. Breast milk samples will be collected for 2 weeks (Day 1, 2, 3, 4, 7, 14) after the establishment of lactation.

Secondary Outcome Measures

Pharmacokinetics - distribution, terminal elimination and absorption half-life(t1/2) of azithromycin and piperaquine

Pharmacokinetics - area under the plasma concentration versus time curve (AUC) of azithromycin and piperaquine

Pharmacokinetics - peak plasma concentration (Cmax) of azithromycin and piperaquine

Pharmacokinetics - clearance (CL) of azithromycin and piperaquine

Pharmacokinetics - volume of distribution (Vd) of azithromycin and piperaquine

PCR adjusted 28 day cure

PCR adjusted 42 day cure

Number of participants with adverse events as a measure of safety and tolerability

Full Information

NCT ID

NCT02575755

First Posted

October 8, 2015

Last Updated

October 14, 2015

Sponsor

Papua New Guinea Institute of Medical Research

Collaborators

The University of Western Australia, University of Melbourne, Malaria in Pregnancy Consortium

1. Study Identification

Unique Protocol Identification Number

NCT02575755

Brief Title

A Safety, Tolerability, Pharmacokinetic and Efficacy Study of Azithromycin Plus Piperaquine as Presumptive Treatment in Pregnant PNG Women

Official Title

A Safety, Tolerability, Pharmacokinetic and Efficacy Study of Azithromycin Plus Piperaquine as Presumptive Treatment in Pregnant Papua New Guinean Women

Study Type

Interventional

2. Study Status

Record Verification Date

October 2015

Overall Recruitment Status

Unknown status

Study Start Date

October 2012 (undefined)

Primary Completion Date

July 2016 (Anticipated)

Study Completion Date

October 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Papua New Guinea Institute of Medical Research

Collaborators

The University of Western Australia, University of Melbourne, Malaria in Pregnancy Consortium

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Plasmodium falciparum parasitaemia in pregnancy is associated with maternal anaemia, low birth-weight and increased perinatal mortality. Whilst continuous prophylaxis is difficult to implement, intermittent presumptive treatment in pregnancy (IPTp) has proved to be practical and effective. In PNG, pregnant women currently receive IPTp using sulfadoxine-pyrimethamine, however, this therapy has the potential to be compromised by parasite resistance. The aim of the present trial is to assess the safety, tolerability, pharmacokinetics and efficacy of azithromycin (AZI) plus piperaquine (PQ) given as IPTp to pregnant Papua New Guinea women. The study will comprise of two sub-studies: (i) A safety, tolerability and pharmacokinetic study of AZI-PQ in pregnancy. (ii) A safety, tolerability and preliminary efficacy study of AZI-PQ in pregnancy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pregnancy, Infections, Plasmodia, Drug Kinetics, Clinical Efficacy

Keywords

Azithromycin, Piperaquine, IPTp, Pharmacokinetics, Efficacy

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Efficacy Study: Azithromycin plus piperaquine

Arm Type

Experimental

Arm Description

At baseline, participants receive three daily doses (0, 24 and 48 hours) of i) 1 g azithromycin as 2 x film-coated 500 mg tablets ii) 960 mg piperaquine tetraphosphate tablets as 3 x 320 mg tablets

Arm Title

Efficacy Study Control: National Standard Treatment

Arm Type

Active Comparator

Arm Description

At baseline, participants receive a single dose of sulfadoxine-pyrimethamine comprising 1,500 mg of sulfadoxine and 75 mg pyrimethamine in tablet form

Arm Title

Pharmacokinetic Study: Azithromycin plus piperaquine

Arm Type

Experimental

Arm Description

At baseline, participants receive three daily doses (0, 24 and 48 hours) of i) 1 g azithromycin as 2 x film-coated 500 mg tablets ii) 960 mg piperaquine tetraphosphate tablets as 3 x 320 mg tablets

Intervention Type

Drug

Intervention Name(s)

Azithromycin plus piperaquine phosphate

Other Intervention Name(s)

Sandoz Azithromycin, Sigma-Tau Piperaquine tetraphosphate

Intervention Type

Drug

Intervention Name(s)

Sulfadoxine-pyrimethamine

Primary Outcome Measure Information:

Title

Efficacy of azithromycin plus piperaquine for the prevention of malaria during pregnancy

Description

Time Frame

42 days intensive follow-up, final end-point at 2 weeks post delivery

Secondary Outcome Measure Information:

Title

Pharmacokinetics - distribution, terminal elimination and absorption half-life(t1/2) of azithromycin and piperaquine

Time Frame

42 days intensive follow-up, final end-point at 2 weeks post delivery

Title

Pharmacokinetics - area under the plasma concentration versus time curve (AUC) of azithromycin and piperaquine

Time Frame

42 days intensive follow-up, final end-point at 2 weeks post delivery

Title

Pharmacokinetics - peak plasma concentration (Cmax) of azithromycin and piperaquine

Time Frame

42 days intensive follow-up, final end-point at 2 weeks post delivery

Title

Pharmacokinetics - clearance (CL) of azithromycin and piperaquine

Time Frame

42 days intensive follow-up, final end-point at 2 weeks post delivery

Title

Pharmacokinetics - volume of distribution (Vd) of azithromycin and piperaquine

Time Frame

42 days intensive follow-up, final end-point at 2 weeks post delivery

Title

PCR adjusted 28 day cure

Time Frame

28 days

Title

PCR adjusted 42 day cure

Time Frame

42 days

Title

Number of participants with adverse events as a measure of safety and tolerability

Time Frame

42 days intensive follow-up, final end-point at 2 weeks post delivery

Other Pre-specified Outcome Measures:

Title

Change in maternal hemoglobin over 28 days

Time Frame

28 days

Title

Change in maternal weight over 28 days

Time Frame

28 days

Title

Infant birth weight

Time Frame

Time of delivery

Title

Maternal parasitaemia

Time Frame

Time of delivery

Title

Placental parasitaemia

Time Frame

Time of delivery

Title

Cord blood parasitaemia

Time Frame

Time of delivery

Title

Maternal hemoglobin at delivery

Time Frame

Time of delivery

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: >14 weeks and <30 weeks gestation No signs of severe malaria by World Health Organisation criteria No significant concomitant disease (such as TB) No prior history of an adverse reaction to AZI or PQP No prior treatment with these drugs in the past 4 weeks Can attend all follow-up visits Provide informed consent Exclusion Criteria: Have signs of severe malaria by WHO criteria Significant concomitant disease such as TB as assessed by the attending clinician A history/family history of sudden death or of congenital prolongation of the QTc interval Any clinical condition known to prolong the QTc interval A history of complicated pregnancies/deliveries A prior history of an adverse reaction to AZI or PQP Have taken these drugs in the past 4 weeks Cannot attend any of the follow-up visits Do not provide informed consent

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Timothy ME Davis, BMedSc MBBS DPhil FRACP MRCP

Phone

(+618) 9431 3229

tim.davis@uwa.edu.au

First Name & Middle Initial & Last Name or Official Title & Degree

Brioni R Moore, BSc, PhD

Phone

(+618) 6151 1172

brioni.moore@uwa.edu.au

Facility Information:

Facility Name

Papua New Guinea Institute of Medical Research

City

Madang

State/Province

Madang Province

ZIP/Postal Code

511

Country

Papua New Guinea

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Brioni R Moore, BSc, PhD

Phone

(+61) 0466266334

brioni.moore@uwa.edu.au

First Name & Middle Initial & Last Name & Degree

Leanne J Robinson, BSc, PhD, MPH

Phone

(+675) 422 2909

robinson@wehi.edu.au

12. IPD Sharing Statement

Learn more about this trial

A Safety, Tolerability, Pharmacokinetic and Efficacy Study of Azithromycin Plus Piperaquine as Presumptive Treatment in Pregnant PNG Women

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