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D5611C00003 - Food Interaction Study With AZD1722 Tablet in Healthy Subjects

Phase 1
Completed
Conditions
Healthy Volunteers Food Interaction Study
Interventions
Drug: AZD1722 salt tablet
Drug: AZD1722 free base tablet
Drug: AZD1722 free base tablet + Omeprazole
Registration Number
NCT02226783
Lead Sponsor
Ardelyx
Brief Summary

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

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)

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
37
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Treatment C AZD1722 salt tablet (fasted)AZD1722 salt tabletPart 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
Treat D AZD1722 free-base tablet (fast)AZD1722 free base tabletPart 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
Treatment B AZD1722 salt tablet (fed)AZD1722 salt tabletPart 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
Treat E AZD1722 free-base+OmeprazoleAZD1722 free base tablet + OmeprazolePart 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
Treatment A AZD1722 salt tablet (fasted)AZD1722 salt tabletPart 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
Treat E AZD1722 free-base+OmeprazoleAZD1722 free base tabletPart 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
Primary Outcome Measures
NameTimeMethod
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 formulationStool samples will be collected over 24 hr periods from day -2 to Day 17

Sodium and phosphorus content in stool collected over 24-hour intervals

Secondary Outcome Measures
NameTimeMethod
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 formulationStool samples will be collected over 24 hr periods from day -2 to Day 17

Stool consistency, weight, and frequency measured on a daily basis

Pharmacokinetic: To evaluate the plasma concentrations of AZD1722Predose, 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

AZD1722 plasma concentrations

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 formulationUrine will be collected in 24 hour intervals from Day -2 to Day 17

Urinary sodium and phosphorus content over 24-hour intervals

Trial Locations

Locations (1)

Research Site

🇺🇸

Overland Park, Kansas, United States

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