HypertensionPhase 1NCT01797926
Study to Determine the Bioequivalence of Two Fixed Dose Combination (FDC) Tablet Formulations of Amlodipine and Losartan FDC5/50 and FDC5/100 Under Fasting Conditions
A Phase 1 study testing Reference Treatment: 5 mg amlodipine + 50 mg losartan, Reference Treatment:5 mg amlodipine + 100 mg losartan and FDC 5/50 amlodipine/ losartan in people with Hypertension, run by GlaxoSmithKline at 1 site in South Africa.
Trial summary
This is a three-period, three sequence, reference replicated, cross-over study to determine the bioequivalence of two amlodipine and losartan FDC tablet formulations FDC5/50 and FDC5/100 (GSK2944406; 5 mg amlodipine and 50 mg and 100 mg losartan) to reference amlodipine and losartan tablets co-administered in two… 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?
- Reference Treatment: 5 mg amlodipine + 50 mg losartan, Reference Treatment:5 mg amlodipine + 100 mg losartan and FDC 5/50 amlodipine/ losartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 1 siteSouth Africa
- Study dates
- 23 May 2013to 25 Jul 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Age \& Gender: Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Body weight >= 50 kg and body mass index (BMI) within the range 18.5 to 24.9 kilogram/meter squared.
- Alanine aminotransferase (ALT) alkaline phosphatase and bilirubin <or=1.5x upper limit of normal (ULN).
- Normal electrocardiogram (ECG) measurements. Average QT duration corrected for heart rate by Fridericia's formula (QTcF) <450 millisecond (msec) or QTcF <480 msec in subjects with Bundle Branch Block based on an average from three ECGs obtained over a brief recording period.
- Female subjects of non-child bearing potential. Females of child bearing potential are eligible to enter if they are not pregnant and willing to use protocol-specified methods of contraception to prevent pregnancy.
- Healthy as determined by a responsible and experienced physician, based on a medical Evaluation.
- Capable of giving written informed consent.
Who cannot join
- The subject has a positive: drug/alcohol screen, Hepatitis, human immunodeficiency virus(HIV) screen
- Subject with systolic blood pressure less than 90 mmHg or diastolic less than 60 mm Hg irrespective of associated symptoms at the time of admission
- If there is a drop in 20 mmHg of systolic pressure (and a 10 mmHg drop in diastolic) and a 20 beats per minute increase in heart rate between supine measurement and after two minutes standing at the time of admission.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol at the time of admission.
- Abuse of alcohol
Show all 18Show fewer
- Participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Donation of more than 500 milliliter (mL) blood within a 56 day period.
- Pregnant or lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- Subject having positive urinary cotinine levels indicative of use of tobacco or nicotine-containing products within 6 months prior to screening.
- Subjects who have asthma or a history of asthma including childhood asthma.
- Unable to refrain from consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Randomised, Single Dose, Three-way Crossover, Parallel Groups Study to Determine the Bioequivalence of Two Fixed Dose Combination (FDC) Tablet Formulations of Amlodipine and Losartan FDC5/50 and FDC5/100 to Respective Reference Dosages in Healthy Adult Male and Female Subjects Under Fasting Conditions
This is a three-period, three sequence, reference replicated, cross-over study to determine the bioequivalence of two amlodipine and losartan FDC tablet formulations FDC5/50 and FDC5/100 (GSK2944406; 5 mg amlodipine and 50 mg and 100 mg losartan) to reference amlodipine and losartan tablets co-administered in two groups enrolling 102 healthy adult male and female subjects under fasting conditions.
A description of each treatment is provided below:
Read more
A (Reference) = 1 x 5 mg amlodipine tablet and 1 x 50 mg losartan tablet. B (FDC5/50) = 1 x 5 mg amlodipine and 50 mg losartan tablet C (Reference) = 1 x 5 mg amlodipine tablet and 1 x 100 mg losartan tablet D (FDC5/100) = 1 x 5 mg amlodipine and100 mg losartan tablet The treatments will be administered in accordance with the randomisation schedule as.
Group 1: A → A → B or A → B → A or B → A → A Group 2: C → C → D or C → D → C or D → C → C All subjects will attend a screening visit within 28 days of their first dosing period (Day 1). The baseline assessments will be conducted the day before the first dosing.
In each treatment period, subjects will be admitted to the clinic in the evening before Day 1. All subjects will receive a single oral dose of amlodipine and losartan in the morning on Day 1. All the subjects will remain in the clinical unit until completion of all assessments at 24 hours post-dose on Day 2 including collection of the 24 hour post-dose PK sample. Subjects will return to the clinic for pharmacokinetic samples at 36, 48, 72 and 96 hours post-dose.
The three treatment periods will be separated by a washout period of 10-17 days. Upon completion of the last dosing period, or early withdrawal, subjects will return to the clinical unit within 14-21 days for a follow up visit.
- Conditions
- Hypertension
- Being tested
- Reference Treatment: 5 mg amlodipine + 50 mg losartan, Reference Treatment:5 mg amlodipine + 100 mg losartan, FDC 5/50 amlodipine/ losartan, FDC 5/100 amlodipine /losartan
- Keywords
- pharmacokinetics, Hypertension, losartan, healthy volunteers, amlodipine
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reference Treatment: 5 mg amlodipine + 50 mg losartanDrug
Subjects will receive 1 x 5 mg amlodipine tablet with 1 x 50 mg losartan tablet administered orally in fasted state as a single dose
Reference Treatment:5 mg amlodipine + 100 mg losartanDrug
Subjects will receive 1 x 5 mg amlodipine tablet with 1 x 100 mg losartan tablet administered orally in fasted state as a single dose
FDC 5/50 amlodipine/ losartanDrug
Subjects will receive single oral dose of 1 tablet containing 5 mg amlodipine and 50 mg losartan in fasted state
FDC 5/100 amlodipine /losartanDrug
Subjects will receive single oral dose of 1 tablet containing 5 mg amlodipine and 100 mg losartan in fasted state
| Study group | Role | What they receive |
|---|---|---|
| Group 1 (5 mg amlodipine and 50 mg losartan) | Experimental | Subjects in Group 1 will be randomized to receive a single dose FDC 5/50 mg tablet and also separate single tablets each of reference treatment 5 mg amlodipine and 50 mg losartan. The reference treatment will be replicated in a three sequence, three period design Receives: Drug: Reference Treatment: 5 mg amlodipine + 50 mg losartan; Drug: FDC 5/50 amlodipine/ losartan |
| Group 2 (5 mg amlodipine and 100 mg losartan) | Experimental | Subjects in Group 2 will be randomized to receive a single dose FDC 5/100 mg; and also separate single tablets each of reference treatment 5 mg amlodipine and 100 mg losartan. The reference treatment will be replicated in a three sequence, three period design Receives: Drug: Reference Treatment:5 mg amlodipine + 100 mg losartan; Drug: FDC 5/100 amlodipine /losartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma pharmacokinetic parameters for amlodipine and losartan in relevant treatments
Pharmacokinetic (PK) parameters for amlodipine and losartan will include the 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), area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time exposure over the dosing and interval area under the plasma concentration time curve (AUC (0- infinity)), and maximum plasma concentration (Cmax)
Measured: Up to 25 days at regular time points
Secondary outcomes (5)
Plasma pharmacokinetic (PK) parameters tmax, Clast, percentage AUCex and t½ for amlodipine and losartan
The PK parameters: time of occurrence of Cmax (tmax), last observed quantifiable concentration (Clast), percentage AUCex and terminal phase half-life (t½) will be determined from the plasma concentration-time data
Measured: Up to 25 Days at regular time points
Plasma Pharmacokinetic parameters for carboxylic acid (active losartan metabolite)
The PK paramenters for carboxylic acid: AUC (0-t), AUC (0-infinity), Cmax, tmax, %AUCex, Clast and t½will be determined from the plasma concentration-time data
Measured: Up to 25 Days at regular time points
Measure of clinical laboratory test values to access safety and tolerability
Clinical laboratory tests will include hematology, clinical chemistry and urinalysis
Measured: Up to 45 Days
Safety assessed by vital sign measurements
Vital sign measurements will include pulse rate and blood pressure
Measured: Up to 45 Days
Number of subjects with adverse events (AE)s
Safety and tolerability parameters will include recording of AEs
Measured: Up to 45 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2013 (estimated)
- Study start23 May 2013
- Primary completion25 Jul 2013
- Study completion25 Jul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 102 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
- NCT01797926
- Sponsor's protocol ID
- 116799
- Status last verified
- Jun 2017
- First submitted
- 21 Feb 2013
- Last updated
- 12 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Randomised, Single Dose, Three-way Crossover, Parallel Groups Study to Determine the Bioequivalence of Two Fixed Dose Combination (FDC) Tablet Formulations of Amlodipine and Losartan FDC5/50 and FDC5/100 to Respective Reference Dosages in Healthy Adult Male and Female Subjects Under Fasting Conditions
- ClinicalTrials.gov ID
- NCT01797926
- Acronym / sponsor ID
- 116799
- Conditions
- Hypertension
- Keywords
- pharmacokinetics, Hypertension, losartan, healthy volunteers, amlodipine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 23 May 2013 (actual)
- Primary completion
- 25 Jul 2013 (actual)
- Study completion
- 25 Jul 2013 (actual)
- First posted
- 25 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a three-period, three sequence, reference replicated, cross-over study to determine the bioequivalence of two amlodipine and losartan FDC tablet formulations FDC5/50 and FDC5/100 (GSK2944406; 5 mg amlodipine and 50 mg and 100 mg losartan) to reference amlodipine and losartan tablets co-administered in two groups enrolling 102 healthy adult male and female subjects under fasting conditions.
A description of each treatment is provided below:
A (Reference) = 1 x 5 mg amlodipine tablet and 1 x 50 mg losartan tablet. B (FDC5/50) = 1 x 5 mg amlodipine and 50 mg losartan tablet C (Reference) = 1 x 5 mg amlodipine tablet and 1 x 100 mg losartan tablet D (FDC5/100) = 1 x 5 mg amlodipine and100 mg losartan tablet The treatments will be administered in accordance with the randomisation schedule as.
Group 1: A → A → B or A → B → A or B → A → A Group 2: C → C → D or C → D → C or D → C → C All subjects will attend a screening visit within 28 days of their first dosing period (Day 1). The baseline assessments will be conducted the day before the first dosing.
In each treatment period, subjects will be admitted to the clinic in the evening before Day 1. All subjects will receive a single oral dose of amlodipine and losartan in the morning on Day 1. All the subjects will remain in the clinical unit until completion of all assessments at 24 hours post-dose on Day 2 including collection of the 24 hour post-dose PK sample. Subjects will return to the clinic for pharmacokinetic samples at 36, 48, 72 and 96 hours post-dose.
The three treatment periods will be separated by a washout period of 10-17 days. Upon completion of the last dosing period, or early withdrawal, subjects will return to the clinical unit within 14-21 days for a follow up visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 (5 mg amlodipine and 50 mg losartan) | Experimental | Drug: Reference Treatment: 5 mg amlodipine + 50 mg losartan, Drug: FDC 5/50 amlodipine/ losartanSubjects in Group 1 will be randomized to receive a single dose FDC 5/50 mg tablet and also separate single tablets each of reference treatment 5 mg amlodipine and 50 mg losartan. The reference treatment will be replicated in a three sequence, three period design |
| Group 2 (5 mg amlodipine and 100 mg losartan) | Experimental | Drug: Reference Treatment:5 mg amlodipine + 100 mg losartan, Drug: FDC 5/100 amlodipine /losartanSubjects in Group 2 will be randomized to receive a single dose FDC 5/100 mg; and also separate single tablets each of reference treatment 5 mg amlodipine and 100 mg losartan. The reference treatment will be replicated in a three sequence, three period design |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age \& Gender: Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Body weight >= 50 kg and body mass index (BMI) within the range 18.5 to 24.9 kilogram/meter squared.
- Alanine aminotransferase (ALT) alkaline phosphatase and bilirubin <or=1.5x upper limit of normal (ULN).
- Normal electrocardiogram (ECG) measurements. Average QT duration corrected for heart rate by Fridericia's formula (QTcF) <450 millisecond (msec) or QTcF <480 msec in subjects with Bundle Branch Block based on an average from three ECGs obtained over a brief recording period.
- Female subjects of non-child bearing potential. Females of child bearing potential are eligible to enter if they are not pregnant and willing to use protocol-specified methods of contraception to prevent pregnancy.
Key exclusion criteria (18 listed)
- The subject has a positive: drug/alcohol screen, Hepatitis, human immunodeficiency virus(HIV) screen
- Subject with systolic blood pressure less than 90 mmHg or diastolic less than 60 mm Hg irrespective of associated symptoms at the time of admission
- If there is a drop in 20 mmHg of systolic pressure (and a 10 mmHg drop in diastolic) and a 20 beats per minute increase in heart rate between supine measurement and after two minutes standing at the time of admission.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol at the time of admission.
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 |
|---|---|---|
| Reference Treatment: 5 mg amlodipine + 50 mg losartanSubjects will receive 1 x 5 mg amlodipine tablet with 1 x 50 mg losartan tablet administered orally in fasted state as a single dose | Drug | Group 1 (5 mg amlodipine and 50 mg losartan) |
| Reference Treatment:5 mg amlodipine + 100 mg losartanSubjects will receive 1 x 5 mg amlodipine tablet with 1 x 100 mg losartan tablet administered orally in fasted state as a single dose | Drug | Group 2 (5 mg amlodipine and 100 mg losartan) |
| FDC 5/50 amlodipine/ losartanSubjects will receive single oral dose of 1 tablet containing 5 mg amlodipine and 50 mg losartan in fasted state | Drug | Group 1 (5 mg amlodipine and 50 mg losartan) |
| FDC 5/100 amlodipine /losartanSubjects will receive single oral dose of 1 tablet containing 5 mg amlodipine and 100 mg losartan in fasted state | Drug | Group 2 (5 mg amlodipine and 100 mg losartan) |
Primary outcome
Plasma pharmacokinetic parameters for amlodipine and losartan in relevant treatments
Time frame: Up to 25 days at regular time points
Pharmacokinetic (PK) parameters for amlodipine and losartan will include the 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), area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time exposure over the dosing and interval area under the plasma concentration time curve (AUC (0- infinity)), and maximum plasma concentration (Cmax)
5 secondary outcomes
Plasma pharmacokinetic (PK) parameters tmax, Clast, percentage AUCex and t½ for amlodipine and losartan
Time frame: Up to 25 Days at regular time points
Plasma Pharmacokinetic parameters for carboxylic acid (active losartan metabolite)
Time frame: Up to 25 Days at regular time points
Measure of clinical laboratory test values to access safety and tolerability
Time frame: Up to 45 Days
Safety assessed by vital sign measurements
Time frame: Up to 45 Days
Number of subjects with adverse events (AE)s
Time frame: Up to 45 Days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2017.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Results for study 116799 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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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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 Reference Treatment: 5 mg amlodipine + 50 mg losartan, Reference Treatment:5 mg amlodipine + 100 mg losartan and FDC 5/50 amlodipine/ losartan 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 7 inclusion and 18 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 12 Jun 2017. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Plasma pharmacokinetic parameters for amlodipine and losartan in relevant treatments (time frame: Up to 25 days at regular time points). 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 12 Jun 2017.