To Evaluate the Effect of AZD1722 on the Pharmacokinetics of Oral Midazolam in Healthy Volunteers

Overview

A Study to Evaluate the Effects of oral repeated doses of AZD1722 on the Pharmacokinetics of Oral Midazolam in Healthy Volunteers

Full Title of Study: “A Phase 1, Single-center, Fixed-sequence, Open Label Study to Evaluate the Effect of Oral Repeated Doses of AZD1722 on the Pharmacokinetics of Oral Midazolam in Healthy Volunteers”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 2014

Detailed Description

A Phase 1, Single-center, Fixed-sequence, Open Label Study to Evaluate the Effect of Oral Repeated Doses of AZD1722 on the Pharmacokinetics of Oral Midazolam in Healthy Volunteers

Interventions

  • Drug: Midazolam
    • Volunteers will receive a single dose of Midazolam 7.5 mg on Day 1
  • Drug: AZD1722
    • Volunteers will receive twice daily, oral doses of AZD1722 15 mg on Days 2-14
  • Drug: AZD1722 and Midazolam
    • On Day 15 volunteers will receive AZD1722 15 mg and Midazolam 7.5 mg at the same time in the morning. In the evening on Day 15 AZD1722 15 mg will be administered alone.

Arms, Groups and Cohorts

  • Active Comparator: Midazolam 7.5 mg
    • Volunteers will receive Midazolam 7.5 mg administered by mouth as a syrup
  • Experimental: AZD1722 15 mg
    • Volunteers will received AZD1722 15 mg administered by mouth, as a tablet
  • Experimental: AZD1722 15 mg and Midazolam 7.5 mg
    • Volunteers will receive AZD1722 15 mg tablet and Midazolam 7.5 mg syrup, by mouth

Clinical Trial Outcome Measures

Primary Measures

  • To evaluate the pharmacokinetics of midazolam when administered after AZD1722 by assessment of area under the concentration-time curve (AUC) and maximal plasma concentration (Cmax) of midazolam
    • Time Frame: Blood samples are collected predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 15 and 24 hours post dose on Day 1 and Day 15
    • Change in plasma area under the concentration-time curve (AUC) and maximal plasma concentration (Cmax) of midazolam after AZD1722 administration

Secondary Measures

  • • To evaluate the pharmacokinetics of the metabolites 1-OH-midazolam and 4-OH-midazolam when midazolam is administered after AZD1722 by assessment of AUC and Cmax of 1-OH-midazolam and 4-OH-midazolam
    • Time Frame: Blood samples are collected predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 15 and 24 hours post dose on Day 1 and Day 15
    • Change in plasma area under the concentration-time curve (AUC) maximal plasma concentration (Cmax) of 1-OH-midazolam and 4-OH-midazolam after AZD1722 administration
  • To evaluate the pharmacodynamic outcomes of AZD1722 by assessment of how AZD1722 effects stool consistency and frequency
    • Time Frame: Stool frequency and stool consistency will be measured daily (Day -1 through Day 16)
    • Pharmacodynamic outcome of the effect on stool consistency and frequency
  • To evaluate the plasma concentrations of AZD1722
    • Time Frame: Blood samples are collected predose, 1, 2, 4 hours post morning dose on Day 15
    • plasma concentrations of AZD1722 to be measured (no PK parameters derived)
  • To evaluate the pharmacokinetics of midazolam metabolites when administered after AZD1722 by assessment of area under the concentration-time curve (AUC) maximal plasma concentration (Cmax) of 1-OH-midazolam and 4-OH-midazolam
    • Time Frame: Blood samples are collected predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 15 and 24 hours post dose on Day 1 and Day 15
    • Change in plasma area under the concentration-time curve (AUC) maximal plasma concentration (Cmax) of 1-OH-midazolam and 4-OH-midazolam after AZD1722 administration

Participating in This Clinical Trial

Inclusion Criteria

Have a body mass index (BMI) ≥18 and ≤30 kg/m2 and weigh at least 50 kg and no more than 100 kg. Females of non-childbearing potential must be postmenopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and follicle stimulating hormone (FSH) levels in the postmenopausal range or documentation of irreversible surgical sterilization by hysterectomy, bilateraloophorectomy or bilateral salpingectomy but not tubal ligation

Females of childbearing potential must have a negative pregnancy test at screening, Day -1, and Day 14 and must not be lactating and use effective contraceptive methods to avoid pregnancy during the treatment period

Male healthy volunteers with a partner of childbearing potential must agree to avoid fathering a child, and refrain from donating sperm, from the first day of dosing until at least 3 months after last dose of the investigational product, and therefore be either sterile or agree to use approved methods of contraception

Exclusion Criteria

  • History of any clinically significant disease or disorder which, in the opinion of the principal investigator, may either put the healthy volunteer at risk because of participation in the study, or influence the results or the healthy volunteer's ability to participate in the study. History or presence of GI, hepatic or renal disease including GI surgery other than appendectomy or any other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. Loose stools (BSFS of 6 or 7) ≥2 days in the past 7 days before investigational product administration. Use of medications that are known to affect stool consistency and/or GI motility, including fiber supplements, anti-diarrheals, prokinetic drugs, enemas, probiotic medications or supplements, or salt or electrolyte supplements containing sodium, potassium, chloride, or bicarbonate formulations during the past 7 days before the investigational product administration. Use of any prescribed or non-prescribed medication including antacids, analgesics other than paracetamol/acetaminophen, herbal remedies, vitamins and minerals during the 2 weeks prior to the first administration of investigational product or longer if the medication has a long half-life. Use of drugs or substances with enzyme-inducing properties within 4 weeks prior to the first administration of investigational product.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 50 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Ardelyx
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Eleanor Lisbon, MD, Principal Investigator, Quintiles, Inc.

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