Drug-Drug Interaction Study to Evaluate the Effect of Colestilan on the Pharmacokinetics of Single Doses of Candesartan Cilexetil in Healthy Subjects
Condition: Hyperphosphatemia; Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Hyperphosphatemia
Intervention: colestilan; candesartan
Intervention MeSH terms: Candesartan; Candesartan cilexetil
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: Male
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: CKD Stage V; dialysis

Summary:

      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.
    

Eligibility criteria:

        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.