Food-Effect Bioavailability Study of AQ-13, a Candidate Antimalarial
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to test the safety of a 2100 mg dose of AQ-13, a new candidate
      antimalarial active against drug-resistant P. falciparum infection, and to determine the
      effect of a standard fatty meal on the absorption of the drug from the gut and its blood
      levels.
    

Detailed description: 
      This is a 2-stage, randomized crossover study of a 2100 mg AQ-13 dose in healthy volunteers.
      Fourteen healthy volunteers will be randomized to receive the drug either on an empty stomach
      or after a standard fatty meal under continuous monitoring in the hospital. After a washout
      period of 8 weeks, the volunteers will be admitted to the hospital again to receive the same
      dose of the drug after a fatty meal or on an empty stomach in reverse - so each volunteer
      will receive AQ-13 with and without a fatty meal.

      Study Population:

      Healthy young men and women, 21-45 years of age who are taking no chronic medications with
      the exception of birth control pills will be invited to participate in this food-effect
      bioavailability study at the Tulane-LSU General Clinical Research Center in New Orleans.
      Exclusion criteria include pregnancy, breast feeding, abnormal liver or kidney function
      tests, anemia (Hb < 12 gm per dL), chronic medications other than birth control pills, and an
      abnormal baseline ECG or Holter recording.

      Randomization:

      Allocation codes will be generated by the biostatistician in blocks, using computer software,
      and will be sealed in numbered, opaque envelopes. Block sizes will be determined at random
      and will not be known to the study personnel. The envelopes containing the randomization
      codes will be hand-delivered to the study pharmacist and kept in the Research Pharmacy, which
      is outside the GCRC.

      Blinding:

      The investigators and laboratory personnel performing the laboratory tests and comparing
      those results, electrocardiograms and Holter recordings for AQ-13 doses will be blinded to
      which AQ-13 doses were administered with or without a fatty meal. However, the volunteers
      themselves and the nursing personnel in the GCRC will know which doses were administered with
      and without a fatty meal. Therefore, this is a single-blinded study.

      Informed Consent:

      Informed consent will be obtained from each participant before screening. According to IRB
      guidelines, the informed consent form will be revised at yearly intervals and whenever new
      information on AQ-13 or its side effects becomes available.

      In-patient Procedures:

      On the evening of admission, pregnancy testing will be repeated and CK will be measured
      before drug administration the following morning. The drug administration protocol will
      follow the design outlined in the FDA "Guidance for Industry" for food-effect bioavailability
      studies (1-2). The 2100 mg AQ-13 dose will be divided into three doses of 700 mg each to be
      administered once a day in the morning on an empty stomach with 240 ml water after 10 hours
      fasting for the empty stomach arm. For the fatty meal arm, the AQ-13 dose on day 1 will be
      administered within 30 minutes of a standard fatty meal, prepared as described in the FDA
      "Guidance" and administered with 240 ml water after 10 hours of fasting. The fatty meal
      should be eaten within 30 minutes and the drug should be administered 30 minutes after start
      of the fatty meal. For both arms, water will not be allowed for 1 hour before or after the
      dose; and food will not be allowed for 4 hours after the dose (2). A small needle with
      plastic tubing and a blood thinner will be placed in the participant's arm and kept in place
      with paper tape to draw blood samples. The participant will then be monitored for heart
      rhythm, using a Holter monitor for four days beginning at the time of the first dose, and
      will have an electrocardiogram taken 4 hours after each dose. The purpose of the cardiac
      monitoring is to test whether the drug affects the QTc interval or the heart rhythm. Three
      24-hr urine samples will be collected starting at the time of the first dose.

      Outpatient follow up:

      After the inpatient studies at the General Clinical Research Center (GCRC), participants will
      be asked to return to the GCRC as outpatients twice per week for 4 weeks to give (5 ml) of
      blood to follow the drug levels in their blood. At the 2 week follow up visit, an
      electrocardiogram, Holter recording, blood testing for hematology and chemistry, and visual
      exam will be done. At the 4 week follow up, an additional ECG and Holter recording will be
      obtained.

      In the second stage of the study, all in-patient and out-patient follow up procedures will be
      the same as in the first stage, except that the study drug will be administered on an empty
      stomach for volunteers who took the drug after a fatty meal in the first stage and vice
      versa. At least an 8 week washout period must pass between participating in the two stages of
      the study.

      References:

        1. http://www.fda.gov/oc/initiatives/hiv/hivguidance.html

        2. http://www.fda.gov/cder/guidance/5194fnl.pdf
    

Intervention name(s): AQ-13
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Drug-resistant malaria; Bioavailability; Food-effect study