Chronic Kidney Disease, Hyperphosphatemia
Conditions
Keywords
CKD Stage V, dialysis
Brief 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.
Interventions
DRUGcolestilan
DRUGcandesartan
Sponsors
Tanabe Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-t of Candesartan | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose | Area under the plasma concentration-time curve from time zero up to the last quantifiable time-point |
| Cmax of Candesartan | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose | Maximum observed plasma concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose | Time of maximum observed plasma concentration |
| T1/2 | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose | Apparent plasma terminal elimination half-life |
Countries
United Kingdom
Participant flow
Recruitment details
Subjects were recruited at Covance from 14th October 2013.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 35.1 years STANDARD_DEVIATION 10.4 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 18 | 10 / 18 | 11 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
AUC0-t of Candesartan
Area under the plasma concentration-time curve from time zero up to the last quantifiable time-point
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose
Population: PK Population: All subjects who receive at least one dose of candesartan and have sufficient interpretable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Candesartan Alone | AUC0-t of Candesartan | 1118 ng*hr/mL | Standard Deviation 249 |
| T-1hr | AUC0-t of Candesartan | 826 ng*hr/mL | Standard Deviation 308 |
| T0hr | AUC0-t of Candesartan | 494 ng*hr/mL | Standard Deviation 127 |
| T+3hr | AUC0-t of Candesartan | 759 ng*hr/mL | Standard Deviation 211 |
Primary
Cmax of Candesartan
Maximum observed plasma concentration
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose
Population: PK Population: All subjects who receive at least one dose of candesartan and have sufficient interpretable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Candesartan Alone | Cmax of Candesartan | 106.7 ng/mL | Standard Deviation 37.9 |
| T-1hr | Cmax of Candesartan | 94.7 ng/mL | Standard Deviation 58.3 |
| T0hr | Cmax of Candesartan | 42.8 ng/mL | Standard Deviation 7 |
| T+3hr | Cmax of Candesartan | 99.5 ng/mL | Standard Deviation 36.9 |
Secondary
T1/2
Apparent plasma terminal elimination half-life
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Candesartan Alone | T1/2 | 13.50 hr | Standard Deviation 3.31 |
| T-1hr | T1/2 | 9.61 hr | Standard Deviation 1.9 |
| T0hr | T1/2 | 10.44 hr | Standard Deviation 2.18 |
| T+3hr | T1/2 | 10.01 hr | Standard Deviation 1.73 |
Secondary
Tmax
Time of maximum observed plasma concentration
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Candesartan Alone | Tmax | 3.00 hr |
| T-1hr | Tmax | 3.00 hr |
| T0hr | Tmax | 5.05 hr |
| T+3hr | Tmax | 2.05 hr |