D5611C00003 - Food Interaction Study With AZD1722 Tablet in Healthy Subjects

Phase I Study in Healthy Subjects to Evaluate the Pharmacodynamics (PD) of AZD1722 Given With and Without Food (Part A) and a 2-way Crossover to Evaluate the PD of AZD1722 Given as a Free-base Tablet With and Without Omeprazole (Part B)

Study to evaluate the effect of intake of food in comparison to fasting condition on pharmacodynamics of AZD1722 following a twice-daily administration of AZD1722 tablet formulation

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers Food Interaction Study
• Intervention / Treatment: Drug: AZD1722 salt tablet; Drug: AZD1722 free base tablet; Drug: AZD1722 free base tablet + Omeprazole

Detailed Description

A Phase I, Open-label, Randomized, Single-center, 3-way Crossover Study in Healthy Subjects to Evaluate the Pharmacodynamics Effects of AZD1722 Administered With and Without Food (Part A) plus a 2-way Crossover in Subjects to Evaluate the Pharmacodynamic Effect of AZD1722 Administered as an AZD1722 Free-base Tablet with and without Omeprazole (Part B)

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, KS 66211
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male and female volunteers aged 18 to 65 years

2. Females of childbearing potential had to have a negative pregnancy test and females of childbearing potential included in the study had to use 2 effective methods of avoiding pregnancy, females of nonchildbearing potential to fulfill 1 of the following criteria:

   1. Postmenopausal, defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatment and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the postmenopausal range
   2. Documentation of irreversible surgical sterilization by hysterectomy, tubal occlusion, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation
3. Had a body mass index (BMI) of 18 and 30 kg/m2, inclusive, and weight at least 50 kg and no more than 100 kg
4. Regular bowel habits of at least 1 stool portion per day.

Exclusion Criteria:

(1) History of clinically-significant disease or disorder (2) History or presence of GI, hepatic, or renal disease, including GI surgery, or any condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. (3) Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks (4) any clinically-significant abnormalities in clinical chemistry, hematology, or urinalysis.

(5) Abnormal vital signs after a 10-minute supine rest, any clinically-significant abnormalities in rhythm, conduction, or morphology of resting ECG (6) Prolonged QTcF greater than 450 ms or shortened QTcF less than 340 ms or family history of long QT syndrome.

(7) Loose stools (Bristol Stool Form Score [BSFS] of 6 or 7) 2 or more days during the 7 days prior to randomization (8) Use of medications that are known to affect stool consistency and/or GI motility, including fiber supplements, probiotic supplements, probiotic supplements in medication form, antidiarrheals, prokinetic drugs, enemas, probiotic medications or supplements (ie, Activia®); or salt or electrolyte supplements containing sodium, potassium, chloride, or bicarbonate formulations during the past 7 days before randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A AZD1722 salt tablet (fasted); Part A-Treatment A: morning dose of AZD1722 salt tablet 5 to 10 minutes before start of intake of breakfast; evening dose 5 to 10 minutes before start of intake of dinner	Drug: AZD1722 salt tablet; AZD1722 will be administered as 14 mg (salt tablet). tablet for oral use. Subjects will receive a 14 mg tablet in the morning and evening on Days 1 to 4 (Period 1), Days 7 to 10 (Period 2), and Days 13 to 16 (Period 3).
Experimental: Treatment B AZD1722 salt tablet (fed); Part A Treatment B: morning dose of AZD1722 salt tablet 30 minutes after start of intake of breakfast; evening dose 30 minutes after start of intake of dinner	Drug: AZD1722 salt tablet; AZD1722 will be administered as 14 mg (salt tablet). tablet for oral use. Subjects will receive a 14 mg tablet in the morning and evening on Days 1 to 4 (Period 1), Days 7 to 10 (Period 2), and Days 13 to 16 (Period 3).
Experimental: Treatment C AZD1722 salt tablet (fasted); Part A Treatment C: morning dose AZD1722 HCl tablet then breakfast served 1 hour after dosing; evening dose 3 hours after start of intake of dinner and 1 hour before the next meal consumption	Drug: AZD1722 salt tablet; AZD1722 will be administered as 14 mg (salt tablet). tablet for oral use. Subjects will receive a 14 mg tablet in the morning and evening on Days 1 to 4 (Period 1), Days 7 to 10 (Period 2), and Days 13 to 16 (Period 3).
Experimental: Treat D AZD1722 free-base tablet (fast); Part B Treatment D: morning dose of AZD1722 free-base tablet administered 5 to 10 minutes before the start of intake of breakfast and evening dose 5 to 10 minutes before start of intake of dinner	Drug: AZD1722 free base tablet; AZD1722 will be given as four 14 mg free-base tablets (56mg) in the morning and evening on Days 1 to 4 (Period 1) and Days 10 to 13 (Period 2).
Experimental: Treat E AZD1722 free-base+Omeprazole; Part B Treatment E: morning dose of AZD1722 free base tablet administered 5 to 10 minutes before start of intake of breakfast and evening dose 5 to 10 minutes before start of intake of dinner; omeprazole was administered twice daily from Days -5 to -1 or Days 5 to 9 (depending on assigned treatment period), 1 hour before breakfast and dinner, and from Days 1 to 4 or Days 10 to 13, 1 hour prior to the administration of AZD1722	Drug: AZD1722 free base tablet; AZD1722 will be given as four 14 mg free-base tablets (56mg) in the morning and evening on Days 1 to 4 (Period 1) and Days 10 to 13 (Period 2).; Drug: AZD1722 free base tablet + Omeprazole; AZD1722 free base tablet administered 5 to 10 minutes before intake of breakfast and evening dose 5 to 10 minutes before start of intake of dinner; omeprazole was administered twice daily from Days -5 to -1 or Days 5 to 9 (depending on assigned treatment period), 1 hour before breakfast and dinner, and from Days 1 to 4 or Days 10 to 13, 1 hour prior to the administration of AZD1722

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamic:- To evaluate the effect of intake of food in comparison to fasting condition on PD of AZD1722 following a twice-daily administration of AZD1722 tablet formulation	Sodium and phosphorus content in stool collected over 24-hour intervals	Stool samples will be collected over 24 hr periods from day -2 to Day 17

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamic:- To evaluate the effect of intake of food in comparison to fasting condition on PD of AZD1722 following twice-daily administration of an AZD1722 tablet formulation	Stool consistency, weight, and frequency measured on a daily basis	Stool samples will be collected over 24 hr periods from day -2 to Day 17
Pharmacodynamic:- To evaluate the effect of intake of food in comparison to fasting condition on PD ofAZD1722 following twice-daily administration of an AZD1722 tablet formulation	Urinary sodium and phosphorus content over 24-hour intervals	Urine will be collected in 24 hour intervals from Day -2 to Day 17
Pharmacokinetic: To evaluate the plasma concentrations of AZD1722	AZD1722 plasma concentrations	Predose, 1, 2, and 4 hours post morning dose for measurement of AZD1722 in plasma will be taken on days 1, 4, 7, 10, 13, and 16

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety:- To evaluate the safety of AZD1722	Adverse events, vital signs, physical examinations, ECGs, and laboratory assessments (chemistry, hematology, and urinalysis)	Safety assessments will be performed throughout the study from Baseline to final follow-up visit (Day-2 to Day 26)
Exploratory:-To evaluate the effect of high and low gastric pH on the PD of AZD1722 following twice daily administration of an AZD1722 free-base tablet formulation given with and without omeprazole	Stool sodium and phosphorus content; stool frequency, weight, and consistency; and urine sodium and phosphorus content assessed over 24-hour intervals	Stool and urine samples will be collected over 24 hr periods from day -2 to Day 14

Collaborators and Investigators

• Sponsor: Ardelyx
• Investigators: Principal Investigator: David Mathews, MD, Quintiles Phase I Services, LLC

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: August 26, 2014
• First Submitted That Met QC Criteria: August 26, 2014
• First Posted (Estimate): August 27, 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: PK; Healthy subjects; Phase I; PD
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: D5611C00003