HypertensionPhase 1NCT03031496
Bioequivalence Study Between GSK3542503 Hydrochlorothiazide + Amiloride Hydrochloride 50 mg: 5 mg Tablets and Reference Product in Healthy Adult Participants Under Fasting Conditions
A Phase 1 study testing GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets) and Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets) in people with Hypertension, run by GlaxoSmithKline at 1 site in South Africa.
Trial summary
The combination of the diuretics amiloride hydrochloride (HCl) and hydrochlorothiazide (HCTZ) (GSK3542503) is indicated for the treatment of hypertension, congestive heart failure and hepatic cirrhosis with ascites and edema. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension
- What is being tested?
- GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets) and Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteSouth Africa
- Study dates
- 17 Mar 2017to 10 Apr 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participants must be between18 and 65 years of age inclusive, at the time of signing the informed consent.
- Healthy, non-smoker, as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the normal reference range for the population being studied may be included only if the investigator in consultation with the medical monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 19-30 kg/meter^2(inclusive).
- Healthy male or female participants
- Male participants must agree to use contraception for 3 days after each dose of study treatment and refrain from donating sperm during that period.
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- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP), or a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study treatment.
- The investigator is responsible for ensuring that male and female study participants understand how to correctly use the methods of contraception.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions.
Who cannot join
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
- Abnormal renal function measured by creatinine clearance.
- Presence of hyperkalemia where the serum potassium is greater than upper limit of normal (ULN).
- History or known acute angle closure glaucoma or ocular complaints, which could increase the risk of ophthalmic reactions as deemed by the investigator.
- Abnormal BP as determined by the investigator.
- Alanine transaminase (ALT) >1.5 times ULN.
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- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percentage).
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- QT interval corrected for heart rate according to Bazett's formula (QTcB) >450 milliseconds (msec). For purposes of data analysis, only QTcB, will be used.
- Past or intended use of over-the-counter or prescription medication including herbal medications, within 14 days prior to dosing. Specific medications listed in protocol of this study may be allowed.
- Where participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 90 days.
- Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
- Current enrolment or past participation within the last 90 days before signing of consent in this or any other clinical study involving an investigational study treatment.
- Presence of hepatitis B surface antigen (HBsAg) at screening, or a positive hepatitis C antibody test result at screening. Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative hepatitis C ribonucleic acid (RNA) test is obtained.
- Positive pre-study drug/alcohol screen.
- Positive human immunodeficiency virus (HIV) antibody test.
- Regular use of known drugs of abuse.
- Sensitivity to heparin or heparin-induced thrombocytopenia.
- Sensitivity to any of the study treatments, or components thereof, or drug or other allergy including allergy to penicillin and sulfonamides that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
- Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of >21 units for males or > 14 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- Participants with any risk as defined in protocol of this study should be excluded from participation in this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Randomized, Single-dose, Two-period Cross-over Study to Evaluate Bioequivalence of GSK3542503 Hydrochlorothiazide + Amiloride Hydrochloride 50 mg: 5 mg Fixed Dose Combination Tablets Versus Reference Product in Healthy Adult Participants Under Fasting Conditions
The combination of the diuretics amiloride hydrochloride (HCl) and hydrochlorothiazide (HCTZ) (GSK3542503) is indicated for the treatment of hypertension, congestive heart failure and hepatic cirrhosis with ascites and edema. This first time in human (FTIH) study is aimed to determine whether the test product GSK3542503 is bioequivalent to the reference (ref) hydrochlorothiazide 50 milligram (mg)/amiloride hydrochlorothiazide 5 mg in healthy adult participants under fasting conditions based on pharmacokinetic (PK) endpoints. This is a phase I, open label, balanced, randomized, single dose, two-way crossover study, enroling approximately 42 healthy participants at a single center. Study participants will be randomized to one of two treatment sequences (A-B or B-A) in accordance with the randomization schedule. A single dose of one of the two treatments A (Test: GSK3542503, a hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination) or B (Reference: Moduretic, a hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination), will be administered on Day 1, in each treatment period. Each participant will participate in both treatment periods and receive a single dose of each treatment. The treatment periods will be separated by a washout period of at least 7 days and no more than 14 days. The total duration in the study for each participant is expected to be 5 to 7 weeks, from screening to his or her last visit. A maximum of 42 participants will be randomized such that at least 32 evaluable participants complete the study.
- Conditions
- Hypertension
- Being tested
- GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets), Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets)
- Keywords
- Cross-over, Hydrochlorothiazide, Amiloride hydrochloride, Phase I, GSK3542503, Bioequivalence, FTIH
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets)Drug
GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets) are cream-colored, circular, flat faced uncoated tablets with beveled edges having break line on one side and "BD" embossed on the other side.
Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets)Drug
Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets) tablets are peach-colored, half scored, diamond shaped tablets marked "MSD917".
| Study group | Role | What they receive |
|---|---|---|
| Test A followed by Ref B of HCTZ 50mg+ Amiloride HCl 5mg | Experimental | Eligible participants following an overnight fast of at least 10 hours, will be administered the study drug orally with 240 mL (8 fluid ounces) of water. No food will be allowed for at least 4 hours post-dose. Water will be allowed as desired except for one hour before and after drug administration. Receives: Drug: GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets); Drug: Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets) |
| Ref B followed by test A of HCTZ 50mg + Amiloride HCl 5mg | Experimental | Eligible participants following an overnight fast of at least 10 hours, will be administered the study drug orally with 240 mL (8 fluid ounces) of water. No food will be allowed for at least 4 hours post-dose. Water will be allowed as desired except for one hour before and after drug administration. Receives: Drug: GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets); Drug: Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Hydrochlorothiazide and Amiloride Hydrochloride
Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent confidence intervals (CIs) for estimates of the geometric mean ratios between the AUC (0-t) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.
Measured: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between the Cmax of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.
Measured: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
Secondary outcomes (14)
AUC From Time Zero to Infinity (AUC[0-inf]) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between the AUC (0-inf) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Median and full range has been presented.
Measured: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
Percentage of AUC(0-inf) Obtained by Extrapolation (Percent AUCex) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between percent AUCex of the test and reference products in relation to the conventional bioequivalence range. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Blood samples were collected at indicated time points under fasting conditions for PK analysis of hydrochlorothiazide and amiloride. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function. Only those participants with data available at the specified time points were analyzed
Measured: Up to 25 days
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
Serum ALT, alk. phosph. and AST levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Day -1 and Day 3 of each treatment period
Blood Urea Nitrogen (BUN) Levels at Indicated Time Points
Serum BUN levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Day -1 and Day 3 of each treatment period
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Serum calcium, chloride, glucose, magnesium, potassium and sodium levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Day -1 and Day 3 of each treatment period
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Serum creatinine, direct bilirubin and total bilirubin levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Day -1 and Day 3 of each treatment period
Total Protein Levels at Indicated Time Points
Serum total protein levels were assessed as a clinical chemistry laboratory parameter at Day -1 and Day 3 in each treatment period. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Day -1 and Day 3 of each treatment period
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
Vital sign measurements including SBP and DBP were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Day -1 and Day 3 of each treatment period
Respiratory Rate Values at Indicated Time Points
Vital sign measurements including respiratory rate were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Day -1 and Day 3 of each treatment period
Pulse Rate Values at Indicated Time Points
Vital sign measurements including pulse rate were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Day -1 and Day 3 of each treatment period
Body Temperature Values at Indicated Time Points
Vital sign measurements including body temperature were taken in a supine position after at least 5 minutes of rest at Day -1, Day 1, Day 2 and Day 3 in each treatment period. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Day -1 and Day 3 of each treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2017 (estimated)
- Study start17 Mar 2017
- Primary completion10 Apr 2017
- Study completion10 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03031496
- Sponsor's protocol ID
- 205694
- Status last verified
- May 2021
- First submitted
- 23 Jan 2017
- Last updated
- 7 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study is available via the Clinical Study Data Request site.
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Randomized, Single-dose, Two-period Cross-over Study to Evaluate Bioequivalence of GSK3542503 Hydrochlorothiazide + Amiloride Hydrochloride 50 mg: 5 mg Fixed Dose Combination Tablets Versus Reference Product in Healthy Adult Participants Under Fasting Conditions
- ClinicalTrials.gov ID
- NCT03031496
- Acronym / sponsor ID
- 205694
- Conditions
- Hypertension
- Keywords
- Cross-over, Hydrochlorothiazide, Amiloride hydrochloride, Phase I, GSK3542503, Bioequivalence, FTIH
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 17 Mar 2017 (actual)
- Primary completion
- 10 Apr 2017 (actual)
- Study completion
- 10 Apr 2017 (actual)
- First posted
- 25 Jan 2017 (estimated)
- Results
- Posted 31 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The combination of the diuretics amiloride hydrochloride (HCl) and hydrochlorothiazide (HCTZ) (GSK3542503) is indicated for the treatment of hypertension, congestive heart failure and hepatic cirrhosis with ascites and edema. This first time in human (FTIH) study is aimed to determine whether the test product GSK3542503 is bioequivalent to the reference (ref) hydrochlorothiazide 50 milligram (mg)/amiloride hydrochlorothiazide 5 mg in healthy adult participants under fasting conditions based on pharmacokinetic (PK) endpoints. This is a phase I, open label, balanced, randomized, single dose, two-way crossover study, enroling approximately 42 healthy participants at a single center. Study participants will be randomized to one of two treatment sequences (A-B or B-A) in accordance with the randomization schedule. A single dose of one of the two treatments A (Test: GSK3542503, a hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination) or B (Reference: Moduretic, a hydrochlorothiazide 50 mg and amiloride hydrochloride 5 mg fixed dose combination), will be administered on Day 1, in each treatment period. Each participant will participate in both treatment periods and receive a single dose of each treatment. The treatment periods will be separated by a washout period of at least 7 days and no more than 14 days. The total duration in the study for each participant is expected to be 5 to 7 weeks, from screening to his or her last visit. A maximum of 42 participants will be randomized such that at least 32 evaluable participants complete the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Test A followed by Ref B of HCTZ 50mg+ Amiloride HCl 5mg | Experimental | Drug: GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets), Drug: Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets)Eligible participants following an overnight fast of at least 10 hours, will be administered the study drug orally with 240 mL (8 fluid ounces) of water. No food will be allowed for at least 4 hours post-dose. Water will be allowed as desired except for one hour before and after drug administration. |
| Ref B followed by test A of HCTZ 50mg + Amiloride HCl 5mg | Experimental | Drug: GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets), Drug: Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets)Eligible participants following an overnight fast of at least 10 hours, will be administered the study drug orally with 240 mL (8 fluid ounces) of water. No food will be allowed for at least 4 hours post-dose. Water will be allowed as desired except for one hour before and after drug administration. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Participants must be between18 and 65 years of age inclusive, at the time of signing the informed consent.
- Healthy, non-smoker, as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the normal reference range for the population being studied may be included only if the investigator in consultation with the medical monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 19-30 kg/meter^2(inclusive).
- Healthy male or female participants
Key exclusion criteria (22 listed)
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
- Abnormal renal function measured by creatinine clearance.
- Presence of hyperkalemia where the serum potassium is greater than upper limit of normal (ULN).
- History or known acute angle closure glaucoma or ocular complaints, which could increase the risk of ophthalmic reactions as deemed by the investigator.
- Abnormal BP as determined by the investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets)GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets) are cream-colored, circular, flat faced uncoated tablets with beveled edges having break line on one side and "BD" embossed on the other side. | Drug | Ref B followed by test A of HCTZ 50mg + Amiloride HCl 5mg, Test A followed by Ref B of HCTZ 50mg+ Amiloride HCl 5mg |
| Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets)Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets) tablets are peach-colored, half scored, diamond shaped tablets marked "MSD917". | Drug | Ref B followed by test A of HCTZ 50mg + Amiloride HCl 5mg, Test A followed by Ref B of HCTZ 50mg+ Amiloride HCl 5mg |
Primary outcome
Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Hydrochlorothiazide and Amiloride Hydrochloride
Time frame: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent confidence intervals (CIs) for estimates of the geometric mean ratios between the AUC (0-t) of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.
Maximum Observed Concentration (Cmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Time frame: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
Blood samples were collected at indicated time points under fasting conditions for pharmacokinetic (PK) analysis of hydrochlorothiazide and amiloride. Bioequivalence of test product and reference product was assessed based on the 90 percent CIs for estimates of the geometric mean ratios between the Cmax of the test and reference products in relation to the conventional bioequivalence range. An analysis of variance was used with sequence, subject (sequence), treatment and period as fixed effects.
14 secondary outcomes
AUC From Time Zero to Infinity (AUC[0-inf]) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Time frame: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
Time of Occurrence of Cmax (Tmax) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Time frame: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
Percentage of AUC(0-inf) Obtained by Extrapolation (Percent AUCex) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Time frame: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
Terminal Phase Half-life (T1/2) of Hydrochlorothiazide and Amiloride Hydrochloride in Plasma
Time frame: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment Period
Time frame: Up to 25 days
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk.Phosph.) and Aspartate Aminotransferase (AST) Levels at Indicated Time Points
Time frame: Day -1 and Day 3 of each treatment period
Blood Urea Nitrogen (BUN) Levels at Indicated Time Points
Time frame: Day -1 and Day 3 of each treatment period
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium Levels at Indicated Time Points
Time frame: Day -1 and Day 3 of each treatment period
Creatinine, Direct Bilirubin and Total Bilirubin Levels at Indicated Time Points
Time frame: Day -1 and Day 3 of each treatment period
Total Protein Levels at Indicated Time Points
Time frame: Day -1 and Day 3 of each treatment period
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Indicated Time Points
Time frame: Day -1 and Day 3 of each treatment period
Respiratory Rate Values at Indicated Time Points
Time frame: Day -1 and Day 3 of each treatment period
Pulse Rate Values at Indicated Time Points
Time frame: Day -1 and Day 3 of each treatment period
Body Temperature Values at Indicated Time Points
Time frame: Day -1 and Day 3 of each treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. IPD for this study is available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK3542503 (HCTZ 50mg/Amiloride HCl 5mg tablets) and Moduretic (HCTZ 50mg/Amiloride HCl 5mg tablets) in people with Hypertension, run by GlaxoSmithKline at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Hydrochlorothiazide and Amiloride Hydrochloride (time frame: Pre-dose, 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10, 12,14, 16 hours post-dose on Day 1, 24 and 36 hours post dose on Day 2 and 48 hours post-dose on Day 3). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2021.