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This study is required to confirm the suitability of a candidate FDC of 16mg candesartan cilexetil/12.5mg HCTZ (GSK587323) formulation for further development and provide data to allow the design of a future pivotal bioequivalence study. This study aims to determine the relative bioavailability of a FDC tablet formulation of 16mg candesartan cilexetil/12.5mg HCTZ relative to the reference product of same fixed dose combination (16mg candesartan cilexetil/12.5mg HCTZ) in healthy adult humans. This will be an open-label, randomised, single dose, two-way crossover study. Each subject will participate in two treatment periods and will be randomized to one of two sequences and administered one of the two treatments, A or B, as per the randomization schedule. The two treatment periods will be separated by a washout period of 7 to 14 days to ensure the candesartan and HCTZ have been effectively eliminated from the subject between dosing occasions. The study will enroll 16 healthy subjects to ensure that 14 subjects complete the study as planned.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1 | Experimental | Participants in this arm will receive treatment A in period 1 and treatment B in period 2. Subjects will receive a single reference FDC tablet of 16mg candesartan cilexetil/12.5mg HCTZ as Treatment A administered orally with 240mL of water and a single 16mg candesartan cilexetil/12.5mg HCTZ FDC tablet (GSK587323) as Treatment B. |
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| Sequence 2 | Experimental | Participants in this arm will receive treatment B in period 1 and treatment A in period 2. Subjects will receive a single reference FDC tablet of 16mg candesartan cilexetil/12.5mg HCTZ as Treatment A administered orally with 240mL of water and a single 16mg candesartan cilexetil/12.5mg HCTZ FDC tablet (GSK587323) as Treatment B. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK587323 | Drug | Single dose of FDC tablet formulation to be taken orally. |
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| Measure | Description | Time Frame |
|---|---|---|
| Composite of PK parameters for candesartan and HCTZ to assess relative bioavailability. | PK parameters include: maximum observed plasma concentration (Cmax), area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC [0-infinite]) and area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC [0-t]). Twenty four blood samples (1x 5mililiter (mL)) will be collected at the specified time points for PK analysis of candesartan and HCTZ. | Pre dose, 0.33, 0.67, 1, 1.33, 1.67, 2.0, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16, 24, 36, and 48hours post dose in each treatment period. |
| Measure | Description | Time Frame |
|---|---|---|
| PK profile of candesartan and HCTZ. | PK parameters included: time to Cmax (tmax), Percentage of AUC (0-infinite) obtained by extrapolation, and apparent terminal phase half-life (t1/2). PK blood samples (1x 5mL)) will be collected at the specified time points for PK analysis of candesartan and HCTZ. | Pre dose, 0.33, 0.67, 1, 1.33, 1.67, 2.0, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16, 24, 36, and 48hours post dose in each treatment period. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Hyderabad | 500 013 | India |
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| Label | URL |
|---|---|
| Results for study 200957 can be found on the GSK Clinical Study Register. | View source |
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 200957 | Study Protocol | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D006852 | Hydrochlorothiazide |
| ID | Term |
|---|---|
| D002740 | Chlorothiazide |
| D001581 | Benzothiadiazines |
| D013449 | Sulfonamides |
| D013450 | Sulfones |
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| FDC of candesartan cilexetil 16 mg and HCTZ 12.5mg | Drug | Single dose of FDC tablet formulation to be taken orally |
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| Vital sign assessment as a measure of safety and tolerability. | Vital sign parameters include: systolic blood pressure, diastolic blood pressure, and pulse rate. At Baseline the average of the last two blood pressures and pulse readings will be recorded. All measurements will be measured in supine position after 5 minutes rest. | Up to 39 days |
| Review of adverse events (AEs) as a measure of safety and tolerability. | An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. All AEs and serious AEs (SAEs) will be collected from the start of dosing with Investigational Product and until the follow-up visit. However, any SAEs related to study participation or concomitant | Up to 39 days |
| Clinical laboratory data assessment as measure of safety and tolerability. | All subjects for all treatments will be evaluated for any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis). | Up to 39 days |
For additional information about this study please refer to the GSK Clinical Study Register |
| 200957 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200957 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200957 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200957 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200957 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200957 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| D013457 |
| Sulfur Compounds |
| D009930 | Organic Chemicals |
| D049971 | Thiazides |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |