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

NCT00323375 | Completed Phase 1

• 5 other identifiers: Don Krogstad, K 0154 (Phase 1)FDA Phase 1 FD R01-001692UR3/CCU 418652U01CI000211R01AI025136
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria

Keywords

Malaria; Aminoquinolines; Drug Resistance; Chloroquine Resistance

Outcome Measures

Primary Outcomes (3)

• Adverse Events (AEs)

  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).

  AEs were recorded at the time of dosing and for the subsequent 4 weeks.

• Pharmacokinetic Profile

  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.

  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.

• Effects on the QTc Interval

  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.

  QT intervals were monitored beginning before the time of dosing and continuing (24 hour continuous recordings) for the subsequent 96 hours.

Secondary Outcomes (2)

• Pharmacokinetic Profile of AQ-13 and Chloroquine Metabolites

  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 incidence of pruritus in patients receiving Chloroquine Metabolites

  This issue was reviewed with all subjects for the time from 1 to 28 days after beginning treatment with AQ-13 or CQ.

Study Arms (2)

AQ-13 (Investigational 4-Aminoquinoline)

EXPERIMENTAL

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

CQ (Chloroquine)

ACTIVE COMPARATOR

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

Interventions

AQ-13 DRUG

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).

AQ-13 (Investigational 4-Aminoquinoline)

Chloroquine (CQ) Treatment DRUG

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).

Also known as: Aralen

CQ (Chloroquine)

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult volunteers from 21 to 45 years of age

You may not qualify if:

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

Sponsors & Collaborators

• Tulane University Health Sciences Center: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Tulane-LSU-Charity Hospital General Clinical Research Center

New Orleans, Louisiana, 70112, United States

Location

MeSH Terms

Conditions

Malaria

Interventions

Chloroquine; Therapeutics

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Donald J. Krogstad, MD

  Tulane University Health Sciences Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: May 5, 2006
• First Posted: May 9, 2006
• Study Start: August 1, 1999
• Primary Completion: June 30, 2005
• Study Completion: August 31, 2005
• Last Updated: December 8, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: These data have been available since the time of publication in 2007.
• Access Criteria: They are available to other investigators.

Locations

US (1)