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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02140268
• Other study ID #: D5613C00003
• Status: Completed
• Phase: Phase 1
• First received: May 14, 2014
• Last updated: September 18, 2015
• Start date: May 2014
• Est. completion date: August 2014

Study information

• Verified date: September 2015
• Source: Ardelyx
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Midazolam
Volunteers will receive a single dose of Midazolam 7.5 mg on Day 1
• AZD1722
Volunteers will receive twice daily, oral doses of AZD1722 15 mg on Days 2-14
• 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.

Locations

Country	Name	City	State
United States	Research Site	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Ardelyx

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)	Yes
Primary	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	No
Secondary	• 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	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No