Drug-Drug Interaction Study to Evaluate the Effect of Colestilan on the Pharmacokinetics of Single Doses of Candesartan Cilexetil in Healthy Subjects

Study Overview
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Brief Summary
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The primary objective is to assess the effects of colestilan on the pharmacokinetic profile of candesartan cilexetil when administered at the same time as, 1 hour before, and 3 hours after the first daily dose of colestilan administered at doses of 5 g three times daily compared to administration of candesartan cilexetil alone, in healthy subjects.

Official Title
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A Randomised, Open-Label, Drug-Drug Interaction Study to Evaluate the Effect of Colestilan on the Pharmacokinetics of Single Oral Doses of Candesartan Cilexetil in Healthy Subjects

Conditions
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Hyperphosphatemia, Chronic Kidney Disease

Intervention / Treatment
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* Drug: colestilan
* Drug: candesartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent to participate in this study, after reading the participant information sheet and informed consent form (ICF), and after having the opportunity to discuss the study with the Investigator or designee. Caucasian male subjects aged 18 to 50 years inclusive. A body mass index (BMI) between 18.0 and 32.0 kg/m2, both inclusive. Healthy subjects, free from any clinically significant illness or disease as determined by their medical history, physical examination, electrocardiogram (ECG), vital signs, biochemistry, haematology, coagulation, urinalysis, and serology. Male subjects, and their partners, agree to use contraception throughout the study duration. Male subjects must use 1 barrier method of contraception and spermicide during the trial, and for 3 months after the last dose of study drug. Male subjects with female partners of child-bearing potential must also agree to use an additional highly effective method of contraception. They must use a condom, and their female partners must use an additional method of contraception (such as cap or diaphragm), unless the subject or his partner has been sterilised, in which case, male subjects must use a condom and spermicide. Exclusion Criteria: Subjects who have had a clinically significant illness within 4 weeks of the start of dose administration, as determined by the Investigator based on abnormal medical history, physical findings, or laboratory values at Screening or Baseline. Unable to swallow colestilan tablets, current and/or history of dysphagia. Current or any history of any of the following gastrointestinal (GI) diseases: intestinal obstruction, chronic or severe constipation, subileus, ileus, intestinal stenosis, intestinal diverticulosis and/or diverticulitis, colitis, GI ulcers, recent major GI surgery, peritonitis, GI bleeding, gastritis, haemorrhoids, or any other severe GI disease. Current or any history of biliary obstruction, cholestasis, or severe hepatic impairment. Current or history of seizure disorders. Current or history of Vitamin K deficiency. Subjects who have any clinically significant allergic disease (excluding non-active hayfever) as determined by the Investigator. Current or recent history (in the last 2 years) of abuse or addiction (tobacco, alcohol, drugs or substances), or weekly alcohol intake of more than 21 units, or a positive alcohol breath test or urine drug screen at Screening or Baseline. One unit is equivalent to a ½ pint (280 mL) of beer, 1 measure (25 mL) of spirits or 1 small glass (125 mL) of wine. Treatment with any drugs or herbal or dietary supplements known to be inhibitors of cytochrome P450 (CYP) 3A4, CYP2C9 or P-glycoprotein, 7 days before dosing and inducers of CYP3A4, CYP2C9, or P-glycoprotein 14 days before dosing. Treatment with H2 antagonist and/or proton pump inhibitors, during 4 weeks before dosing. Subjects with a history of hypotension or hyperkalaemia, or a postural drop of systolic blood pressure ≥20 mmHg at Screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Candesartan alone<br>Single dose of 16 mg candesartan was administered orally on Day 1. | Drug: candesartan<br> <br> |
| Active Comparator: T0hr<br>Colestilan was administered orally 5 g t.i.d (total dose 15 g/day) in the fed state immediately after meals from Day 3 to Day 24 and single dose of 16 mg candesartan was administered orally on Day 7, 13 and 19 at 1 of 3 dosing time-points relative to the first daily dose of 5 g colestilan t.i.d. T-0 of 3 dosing time-points means the single dose of candesartan was administered at the same time relative to the first daily dose of colestilan. | Drug: colestilan<br> <br> * Other names: BindRen;Drug: candesartan<br> <br> |
| Active Comparator: T-1hr<br>Colestilan was administered orally 5 g t.i.d (total dose 15 g/day) in the fed state immediately after meals from Day 3 to Day 24 and single dose of 16 mg candesartan was administered orally on Day 7, 13 and 19 at 1 of 3 dosing time-points relative to the first daily dose of 5 g colestilan t.i.d. T-1 of 3 dosing time-points means the single dose of candesartan was administered at 1 hour before relative to the first daily dose of colestilan. | Drug: colestilan<br> <br> * Other names: BindRen;Drug: candesartan<br> <br> |
| Active Comparator: T+3hr<br>Colestilan was administered orally 5 g t.i.d (total dose 15 g/day) in the fed state immediately after meals from Day 3 to Day 24 and single dose of 16 mg candesartan was administered orally on Day 7, 13 and 19 at 1 of 3 dosing time-points relative to the first daily dose of 5 g colestilan t.i.d. T+3 of 3 dosing time-points means the single dose of candesartan was administered at 3 hour after relative to the first daily dose of colestilan. | Drug: colestilan<br> <br> * Other names: BindRen;Drug: candesartan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-t of Candesartan | Area under the plasma concentration-time curve from time zero up to the last quantifiable time-point | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose | 
| Cmax of Candesartan | Maximum observed plasma concentration | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | Time of maximum observed plasma concentration | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose | 
| T1/2 | Apparent plasma terminal elimination half-life | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CKD Stage V, dialysis