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

NCT02140268 | Completed Phase 1

• 1 other identifier: D5613C00003
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteers

Keywords

Phase I; Healthy; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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

  Change in plasma area under the concentration-time curve (AUC) and maximal plasma concentration (Cmax) of midazolam after AZD1722 administration

  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

Secondary Outcomes (4)

• • 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

  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

• To evaluate the pharmacodynamic outcomes of AZD1722 by assessment of how AZD1722 effects stool consistency and frequency

  Stool frequency and stool consistency will be measured daily (Day -1 through Day 16)

• To evaluate the plasma concentrations of AZD1722

  Blood samples are collected predose, 1, 2, 4 hours post morning dose on Day 15

• 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

  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

Other Outcomes (1)

• To evaluate the safety of AZD1722 when administered with midazolam in terms of adverse events, vital signs, electrocardiogram (ECG), hematology, clinical chemistry, urinalysis and physical examination

  Safety assessments performed through the screening period (Day -28) to 10 days after the last dose (Day 16)

Study Arms (3)

Midazolam 7.5 mg

ACTIVE COMPARATOR

Volunteers will receive Midazolam 7.5 mg administered by mouth as a syrup

Drug: Midazolam

AZD1722 15 mg

EXPERIMENTAL

Volunteers will received AZD1722 15 mg administered by mouth, as a tablet

Drug: AZD1722

AZD1722 15 mg and Midazolam 7.5 mg

EXPERIMENTAL

Volunteers will receive AZD1722 15 mg tablet and Midazolam 7.5 mg syrup, by mouth

Drug: AZD1722 and Midazolam

Interventions

Midazolam DRUG

Volunteers will receive a single dose of Midazolam 7.5 mg on Day 1

Midazolam 7.5 mg

AZD1722 DRUG

Volunteers will receive twice daily, oral doses of AZD1722 15 mg on Days 2-14

AZD1722 15 mg

AZD1722 and Midazolam DRUG

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.

AZD1722 15 mg and Midazolam 7.5 mg

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ardelyx: lead

Study Sites (1)

Research Site

Overland Park, Kansas, United States

Location

MeSH Terms

Interventions

Midazolam; tenapanor

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Eleanor Lisbon, MD

  Quintiles, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2014
• First Posted: May 16, 2014
• Study Start: May 1, 2014
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: September 22, 2015

Record last verified: 2015-09

Locations

US (1)