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Studies of AQ-13, a Candidate Aminoquinoline Antimalarial, in Comparison With Chloroquine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00323375
Recruitment Status : Completed
First Posted : May 9, 2006
Last Update Posted : December 8, 2020
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Tulane University ( Tulane University Health Sciences Center )

Brief Summary:
The purpose of this protocol is to perform Phase 1 (safety/toxicity and pharmacokinetic) Studies of an investigational aminoquinoline antimalarial (AQ-13) in human subjects. The compound to be studied (AQ-13) is being examined because it is active in vitro against Plasmodium falciparum malaria parasites resistant to chloroquine (CQ) and other antimalarials (multi-resistant P. falciparum), and because its safety was similar to that of CQ in preclinical studies performed by SRI International (IND 55,670). AQ-13 was also selected for study because it is active in vivo in two monkey models of human malaria: 1] P. cynomolgi in the rhesus monkey (Macaca mulatta), a model of human infection with P. vivax, and 2] CQ-resistant P. falciparum in the squirrel monkey, a model of human infection with CQ-resistant P. falciparum.

Condition or disease Intervention/treatment Phase
Malaria Drug: AQ-13 Drug: Chloroquine (CQ) Treatment Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 122 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Individual subjects were randomized to receive either the investigational candidate 4-aminoquinoline (AQ-13) or the control 4-aminoquinoline which has been used to treat malaria for decades and is known to be safe (chloroquine=CQ).
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Subjects randomized to either the AQ-13 or CQ arms of the study received 2 capsules of AQ-13 or CQ in the morning of day 1, 2 capsules of AQ-13 or CQ again on the morning of day 2 and 1 capsule of AQ-13 or CQ on the morning of day 3.
Primary Purpose: Basic Science
Official Title: Randomized Controlled Trial of AQ-13, a Candidate Aminoquinoline Antimalarial, in Comparison With Chloroquine
Actual Study Start Date : August 1, 1999
Actual Primary Completion Date : June 30, 2005
Actual Study Completion Date : August 31, 2005


Arm Intervention/treatment
Experimental: AQ-13 (Investigational 4-Aminoquinoline)
Arm: Experimental: AQ-13 AQ-13 capsules with 350 mg AQ-13 base per capsule. Two capsules orally on days 1 and 2, one capsule orally on day 3.
Drug: AQ-13
A treatment dose of AQ-13 (1750 mg base) was administered orally to subjects randomized to AQ-13 over 3 days (as two capsules on days 1 and 2, plus one capsule on day 3).

Active Comparator: CQ (Chloroquine)
Arm: Active Comparator: CQ CQ Capsules with 300 mg CQ base per capsule per capsule. Two capsules orally on days 1 and 2, one capsule orally on day 3.
Drug: Chloroquine (CQ) Treatment
A treatment dose of CQ (1500 mg CQ base) was administered orally to subjects randomized to CQ over 3 days (as two capsules on days 1 and 2, and one capsule on day 3).
Other Name: Aralen




Primary Outcome Measures :
  1. Adverse Events (AEs) [ Time Frame: AEs were recorded at the time of dosing and for the subsequent 4 weeks. ]
    AEs were recorded in diaries provided to study participants and were used for the 4 week period after dosing with AQ-13 or CQ. Based on those diaries, AEs were graded as mild or serious and from 1 to 4 based on the criteria developed by the Division of AIDS at NIAID (https://rsc.tech-res.com/docs/default-source/safety/daids-ae-grading-table-mar2017.pdf).

  2. Pharmacokinetic Profile [ Time Frame: Blood levels of the parent compounds (CQ and AQ-13) were measured in 5 ml venous blood samples obtained at the time treatment began with CQ or AQ-13 and at 1, 2, 4, 6, 12, 18, 24, 48, 72 and 96 hours thereafter and twice-weekly for the next 4 weeks. ]
    Blood levels of the parent compounds (AQ-13 and CQ) were measured using the assay referenced below in J Chromatogr B which was developed for this purpose.

  3. Effects on the QTc Interval [ Time Frame: QT intervals were monitored beginning before the time of dosing and continuing (24 hour continuous recordings) for the subsequent 96 hours. ]
    Effects of treatment with AQ-13 or CQ on the QT interval were measured by performing Holter monitoring and interpreted in relation to the blood levels of AQ-13 or CQ at the times when the blood samples were obtained.


Secondary Outcome Measures :
  1. Pharmacokinetic Profile of AQ-13 and Chloroquine Metabolites [ Time Frame: These assays began before the time of dosing and continued for 4 weeks after the dosing of AQ-13 and CQ had been completed. ]
    The metabolites of AQ-13 and CQ were monitored (measured) using the same HPLC assay used to measure AQ-13 and CQ because that assay also distinguishes the mono- and di-dealkylated metabolites of AQ-13 and CQ.

  2. The incidence of pruritus in patients receiving Chloroquine Metabolites [ Time Frame: This issue was reviewed with all subjects for the time from 1 to 28 days after beginning treatment with AQ-13 or CQ. ]
    Because pruritus has been reported in subjects receiving CQ, it was considered (discussed) with all patients who received either AQ-13 or CQ.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adult volunteers from 21 to 45 years of age

Exclusion Criteria:

  • Chronic medications with the exception of oral contraceptives Pregnancy Breast-feeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00323375


Locations
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United States, Louisiana
Tulane-LSU-Charity Hospital General Clinical Research Center
New Orleans, Louisiana, United States, 70112
Sponsors and Collaborators
Tulane University Health Sciences Center
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Donald J. Krogstad, MD Tulane University Health Sciences Center
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Responsible Party: Tulane University Health Sciences Center
ClinicalTrials.gov Identifier: NCT00323375    
Other Study ID Numbers: Don Krogstad, K 0154 (Phase 1)
FDA Phase 1 FD R01-001692 ( Other Grant/Funding Number: Food and Drug Administration )
UR3/CCU 418652 ( Other Grant/Funding Number: Centers for Disease Control )
U01CI000211 ( U.S. NIH Grant/Contract )
R01AI025136 ( U.S. NIH Grant/Contract )
First Posted: May 9, 2006    Key Record Dates
Last Update Posted: December 8, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Yes. Send request to Corresponding author (DJ Krogstad) followed by review and approval from the Tulane Biomedical IRB.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: These data have been available since the time of publication in 2007.
Access Criteria: They are available to other investigators.
Keywords provided by Tulane University ( Tulane University Health Sciences Center ):
Malaria
Aminoquinolines
Drug Resistance
Chloroquine Resistance
Additional relevant MeSH terms:
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Malaria
Protozoan Infections
Parasitic Diseases
Infections
Vector Borne Diseases
Chloroquine
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antimalarials
Antirheumatic Agents