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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Midazolam; Drug: AZD1722; Drug: AZD1722 and Midazolam

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

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Midazolam 7.5 mg; Volunteers will receive Midazolam 7.5 mg administered by mouth as a syrup	Drug: Midazolam; Volunteers will receive a single dose of Midazolam 7.5 mg on Day 1
Experimental: AZD1722 15 mg; Volunteers will received AZD1722 15 mg administered by mouth, as a tablet	Drug: AZD1722; Volunteers will receive twice daily, oral doses of AZD1722 15 mg on Days 2-14
Experimental: AZD1722 15 mg and Midazolam 7.5 mg; Volunteers will receive AZD1722 15 mg tablet and Midazolam 7.5 mg syrup, by mouth	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
• 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	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	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	Pharmacodynamic outcome of the effect on 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	plasma concentrations of AZD1722 to be measured (no PK parameters derived)	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	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	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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)

Collaborators and Investigators

• Sponsor: Ardelyx

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: May 14, 2014
• First Submitted That Met QC Criteria: May 14, 2014
• First Posted (Estimate): May 16, 2014

Study Record Updates

• Last Update Posted (Estimate): September 22, 2015
• Last Update Submitted That Met QC Criteria: September 18, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Healthy; Pharmacokinetics; Phase I
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: D5613C00003