Studies of a Candidate Aminoquinoline Antimalarial (AQ-13)

June 18, 2024 updated by: Tulane University

Phase 2 Proof of Concept Study of a Candidate Aminoquinoline Antimalarial (AQ-13)

This is an initial efficacy study of a candidate antimalarial in human subjects with uncomplicated malaria caused by the most common and most important parasite in Africa (Plasmodium falciparum). This study will enroll 66 adult Malian males with uncomplicated P. falciparum malaria and randomize them to treatment with 1750 mg of the investigational drug (AQ-13) by mouth over 3 days or the current standard treatment, which is 2 doses of Coartem twice daily for 3 days. The hypothesis underlying this study is that AQ-13 will be similarly effective to Coartem for the treatment of uncomplicated P. falciparum malaria due to both chloroquine-susceptible and chloroquine-resistant parasites. Funding Source - FDA Office of Orphan Product Development (OOPD).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is an initial efficacy study (Phase 2 Proof of Concept Study) of a candidate antimalarial in human subjects with uncomplicated malaria caused by the most common and most important parasite in Africa (Plasmodium falciparum). This study will enroll 66 adult Malian males with uncomplicated P. falciparum malaria and randomize them to treatment with 1750 mg of the investigational drug (AQ-13) by mouth over 3 days or the current standard treatment, which is 80 mg of artemether and 480 mg of lumefantrine twice daily for 3 days. The hypothesis underlying this study is that AQ-13 will be similarly effective to Coartem for the treatment of uncomplicated P. falciparum malaria due to both chloroquine-susceptible and chloroquine-resistant parasites.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
66

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mali
      • Bamako, Mali, BP 1805
        • Clinical Research Center (Hopital Point G, University of the Sciences, Techniques and Technologies of Bamako)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. Adult Malian males ≥ 18 years of age,
  2. Uncomplicated malaria with ≥ 2,000 asexual P. falciparum parasites per ul, and
  3. Informed consent obtained and signed.

Exclusion Criteria

  1. Severe or complicated malaria (including temperature ≥ 40o C),
  2. ≥ 100,000 asexual parasites per ul of blood,
  3. Anemia or other laboratory results (other than malaria) that require treatment (e.g., Hb ≤ 7 gm/dL, K+ ≤ 3.5 millimolar (mM), BP ≥ 140/90),
  4. Seizures or impaired consciousness,
  5. Recent antimalarial treatment by history (within ≤ 2 weeks),
  6. Chronic medications (including inducers of Cytochrome P450 3A4 [CYP3A4] activity such as rifampin and nevirapine),
  7. Ventricular or atrial arrhythmias, or second or third degree heart block on the screening ECG or Holter recording,
  8. Infection with other plasmodial species on the blood smear (P. ovale, P. ovale, P. vivax).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AQ-13
Adult Malian males 18 years of age or older with uncomplicated P. falciparum malaria who agree to participate and provide their informed consent will be randomized to receive treatment with either AQ-13 or Coartem. Intervention 'AQ-13 Treatment' Participants randomized to the AQ-13 arm will be treated with two (350 mg) capsules on days 1 and 2 and one (350 mg) AQ-13 capsule on day 3 for a total oral dose of 1750 mg of AQ-13 (5 capsules containing 350 mg apiece) over 3 days.
Drug: AQ-13 Treatment
Adult Malian males 18 years of age or older with uncomplicated P. falciparum malaria who agree to participate and provide their informed consent will be randomized to receive treatment with either AQ-13 or Coartem. Intervention 'AQ-13 Treatment' Participants randomized to the AQ-13 arm will be treated with two (350 mg) capsules on days 1 and 2 and one (350 mg) AQ-13 capsule on day 3 for a total oral dose of 1750 mg of AQ-13 (5 capsules containing 350 mg apiece) over 3 days.
Other Names:
  • N'-(7-Chloroquinolin-4-yl)-N,N-diethyl-propane-1,3-diamine.
Active Comparator: Coartem Treatment
Adult Malian males 18 years of age or older with uncomplicated P. falciparum malaria who agree to participate and provide their informed consent will be randomized to receive treatment with either AQ-13 or Coartem. Intervention: Active Comparator: Coartem. Participants randomized to the Coartem arm will be treated with 80 mg artemether and 480 mg lumefantrine at the time of diagnosis and 8 hours later on day 1, the same doses (80 mg artemether and 480 mg lumefantrine) twice on day 2 (24 and 36 hours after diagnosis) and twice more on day 3 (48 and 60 hours after diagnosis) for total oral doses of 480 mg artemether and 2880 mg lumefantrine over 3 days.
Drug: Coartem Treatment
Adult Malian males 18 years of age or older with uncomplicated P. falciparum malaria who agree to participate and provide their informed consent will be randomized to receive treatment with either AQ-13 or Coartem. Intervention 'Coartem Treatment' Participants randomized to the Coartem arm will receive six doses of Coartem tablets over 3 days (each dose containing 80 mg artemether and 480 mg lumefantrine). Those six doses will be given at the time of diagnosis and 8 hours later on day 1, at 24 and 36 hours on day 2 and at 48 and 60 hours on day 3 for total doses of 480 mg artemether and 2880 mg lumefantrine over 3 days.
Other Names:
  • Tablets contain 20 (or 80) mg artemether and 120 (or 480) mg lumefantrine.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cure Rates of AQ-13 and Coartem for Uncomplicated Plasmodium Falciparum Malaria in Adult Malian Males.
Time Frame: Subjects are followed for 42 days after beginning treatment with either AQ-13 or Coartem..
Cure rate is defined as a lack of recrudescence within 42 days PCR-corrected (correcting for new infections due to treatment failures). The investigators were looking for no evidence of recurrent infection with the same parasite genotype after reduction of the asexual parasitemia to less than 25% of the admission value by day 3 and clearance of asexual parasites and fever by day 7 to measure the cure rate. Failure is defined as lack of cure.
Subjects are followed for 42 days after beginning treatment with either AQ-13 or Coartem..

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events
Time Frame: Within 4 weeks of beginning treatment with either AQ-13 or Coartem
Adverse events (AEs) are defined as events possibly related to the study drug(s) as judged by blinded physician observers that occur within 4 weeks of beginning treatment with AQ-13 or Coartem. The investigators asked participants to report the less serious adverse events (≤ grade 1) and the grade 2-4 adverse events and counted the number of participants who had those adverse events happen.
Within 4 weeks of beginning treatment with either AQ-13 or Coartem
Parasite Clearance Time
Time Frame: From the time of beginning treatment with either AQ-13 or Coartem to the first of 2 successive negative blood smears, assessed during the 1 week inpatient stay.
Blood smears are performed at the time of diagnosis and then (for persons who have been enrolled after providing their informed consent to participate) twice daily until two successive negative smears have been obtained.
From the time of beginning treatment with either AQ-13 or Coartem to the first of 2 successive negative blood smears, assessed during the 1 week inpatient stay.
Number of Participants With Recrudescence of Infection
Time Frame: Within 42 days after beginning treatment with either AQ-13 or Coartem
Recrudescence of infection with malaria is the reactivation of the disease after treatment due to incomplete eradication of the parasite, Plasmodium. The parasites causing these recurrences had the same molecular markers as the original infections in these participants, they were considered recrudescences (late treatment failures) rather than new infections. The investigators counted the number of participants who had recrudescence of infection.
Within 42 days after beginning treatment with either AQ-13 or Coartem
QTc Interval Response Following Antimalarial Treatment
Time Frame: Between dosing and 4 hours after dosing
Corrected QT (QTc) interval was measured at antimalarial dosing and at 4 hours after dosing using HolterCare (version 10.6.0) monitors.
Between dosing and 4 hours after dosing
Mean Fever Clearance Time in Days
Time Frame: Days 1-7 after beginning treatment with either AQ-13 or Coartem
Body temperature was measured twice daily with an electronic (digital) thermometer during the 5-7 day inpatient stay. Fever clearance time was defined as the first persistently normal temperature (<37·5°C) during week 1 of inpatient stay.
Days 1-7 after beginning treatment with either AQ-13 or Coartem
Peak Cmax
Time Frame: 42 Days
One of the pharmacokinetic parameters for AQ-13 that was measured was Peak Cmax (Cmax=maximal concentration) which was calculated based on serial blood levels (35 blood level determinations of AQ-13 and its metabolites over the 42 day study period) and urine collections (24 hour collections for the first four days after beginning treatment).
42 Days
Time to Peak Tmax
Time Frame: 42 days
One of the pharmacokinetic parameters for AQ-13 that was measured was time to peak tmax (tmax is time from beginning treatment to the maximal concentration), which was calculated based on serial blood levels (35 blood level determinations of AQ-13 and its metabolites over the 42 day study period) and urine collections (24 hour collections for the first four days after beginning treatment).
42 days
1-week AUC
Time Frame: 42 days
One of the pharmacokinetic parameters for AQ-13 that was measured was 1-week area under the curve (AUC) for the first 7 days, which was calculated based on serial blood levels (35 blood level determinations of AQ-13 and its metabolites over the 42 day study period) and urine collections (24 hour collections for the first four days after beginning treatment).
42 days
Mean Residence Time
Time Frame: 42 Days
One of the pharmacokinetic parameters for AQ-13 that was measured was Mean Residence Time (MRT), which was calculated based on serial blood levels (35 blood level determinations of AQ-13 and its metabolites over the 42 day study period) and urine collections (24 hour collections for the first four days after beginning treatment).
42 Days
Clearance
Time Frame: 42 Days
One of the pharmacokinetic parameters for AQ-13 that was measured was clearance (Cl/f), which was calculated based on serial blood levels (35 blood level determinations of AQ-13 and its metabolites over the 42 day study period) and urine collections (24 hour collections for the first four days after beginning treatment).
42 Days
Elimination t½
Time Frame: 42 Days
One of the pharmacokinetic parameters for AQ-13 that was measured was elimination t½ (t½=elimination half-life) which was calculated based on serial blood levels (35 blood level determinations of AQ-13 and its metabolites over the 42 day study period) and urine collections (24 hour collections for the first four days after beginning treatment).
42 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tulane University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of the Sciences, Techniques and Technologies of Bamako

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Donald J. Krogstad, MD, Tulane School of Public Health and Tropical Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 6, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2012

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 8, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 11, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 18, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2149
  • FDA 1R01-FD-003373 (Other Grant/Funding Number: FDA Office of Orphan Products Development)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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