HypertensionPhase 1NCT00508365
Evaluation of Potential for Orthostatic Hypotension in Elderly Hypertensives
A Phase 1 study testing Carvedilol CR capsules and Lisinopril in people with Hypertension, run by GlaxoSmithKline at 20 sites in United States.
Trial summary
This is a multi-center, double-blind, randomized, placebo-controlled, 2-session crossover study to evaluate the incidence of orthostatic hypotension in elderly hypertensive subjects following co-administration of carvedilol CR and lisinopril. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Hypertension
- What is being tested?
- Carvedilol CR capsules and Lisinopril
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 20 sitesUnited States
- Study dates
- 25 Sep 2007to 3 Jun 2008
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Males or females who are ≥ 65 years of age
- Body mass index (BMI) between 24 and 37 kg/m2 where: BMI = (weight in kg)/ (height in meters)2
- Subjects must have a documented history of essential hypertension and must be stable on treatment with an ACE inhibitor or angiotensin II receptor antagonist or renin antagonist and no more than one other antihypertensive medication at least 3 months before screening with a sitting SBP<180 mmHg and DBP<110 mmHg.
- All subjects must be able to be safely (in the opinion of the Investigator) withdrawn or down-titrated from all antihypertensive treatment(s) and transitioned to lisinopril 10 mg OD for the two-week run-in phase.
Who cannot join
- Any clinically relevant abnormality identified on the screening history, physical or laboratory examination, or any other medical condition or circumstance making the volunteer unsuitable for participation in the study
- Subject who metabolizes carvedilol poorly based on CYP2D6 genotype as determined at screening
- Subject has persistent hyperkalemia or history of hyperkalemia resulting from either Type IV RTA (renal tubular acidosis) or previous treatment with an ACE inhibitor, ARB or renin inhibitor.
- Subject has malignant (accelerated) hypertension, history of malignant hypertension, or history of secondary forms of hypertension
- Subject has advanced hypertensive retinopathy (Keith Wagner Grade IV)
- Subject has a history of hepatic impairment (characterized by prolonged prothrombin time/low concentrations of albumin) and/or renal insufficiency (subjects with an estimated CrCl ≤ 30 mL/min by Cockroft-Gault must be excluded). CrCL = [140-ageCr][weight/70] x 0.85 (if female); Cr in mg/dL; Weight in kg
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- Subject is being treated for diabetes mellitus
- Subject has a history of angioedema
- Subject has been under treatment with 3 or more antihypertensive medications. (NOTE: A combination drug containing two antihypertensive agents represents two antihypertensive medications.)
- Subject has been under treatment with HCTZ > 12.5 mg/day
- Subject is receiving ongoing treatment or is anticipated to receive treatment with any of the following medications during the study:
- monoamine oxidase inhibitors (MAO)
- any Class I or III antiarrhythmic
- alpha-adrenergic receptor blockers
- beta-2-adrenergic agonists
- all antidepressants including SSRIs
- lithium
- medications known to be inhibitors/inducers of cytochrome P-450 2D6 should be discontinued for at least 14 days or 5 half-lives [which ever is longer] prior to the first day of the run-in period
- Treatment with any over-the-counter medications , herbal and dietary supplements, as well as grapefruit-containing products within 7 days or 5 half-lives (whichever is longer) prior to first day of run-in period through the end of the study unless approved by the PI and GSK medical monitor. Standard vitamins and/or daily multi-vitamins are permitted, however herbal vitamins should be excluded.
- Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the run-in period
- Subject has mean sitting SBP ≥ 180 mmHg at the screening assessment (one set of repeat measurement is permitted as per approval by the medical monitor).
- Documented history of low blood pressure within six months of screening visit (average sitting SBP < 110 mm Hg and/or DBP /< 50 mm Hg) or blood pressure below these values at time of screening (one set of repeat measurement is permitted as per approval by the medical monitor).
- Orthostatic hypotension diagnosed at screening (orthostatic hypotension is defined as a reduction in systolic blood pressure of 20 mmHg or more and/or a reduction in diastolic blood pressure of 10 mmHg or more for standing vs. supine measurements)
- Subject has any of the following conditions:
- uncontrollable or symptomatic arrhythmias; unstable angina
- sick sinus syndrome or second or third degree heart block (unless treated with a permanent, functioning pacemaker)
- bradycardia (seated heart rate <55 bpm) (one repeat measurement is permitted as per approval by the medical monitor) ; history of myocardial infarction, or history of stroke within 1 year of screening.
- subject is in, or has a history of atrial fibrillation
- Any of the following abnormalities on 12-lead ECG during screening:
- complete RBBB or LBBB
- evidence of second- or third-degree AV block
- pathological Q-waves (Q-wave wider than 0.04 sec or depth greater than 0.4-0.5 mV)
- any other abnormalities that investigator feels could be of concern when patient is taking a β-adrenergic blocking agent
- Donation of blood in excess of 500 mL within a 56-day period including the estimated 150 mL of blood to be drawn during this study
- History of asthma, COPD and/or hypersensitivity to β -adrenergic blocking agents
- History of sensitivity to carvedilol, lisinopril, alpha-blockers, beta-blockers or ACE inhibitors
- History of sensitivity to any of the study medications or components thereof
- History of anaphylaxis or anaphylactoid reactions or severe allergic responses to drugs
- History of regular alcohol consumption exceeding 7 drinks/week for women or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months of screening
- Unanticipated positive urine drug screen (UDS) at screening. Note: If the subject is taking a drug known to give a positive on the UDS, then this should be discussed with the medical monitor prior to sending the UDS. In this situation, with prior approval, a positive finding on the UDS will not be considered an exclusion
- Positive for Hepatitis B surface antigen or HIV
- Unwillingness or inability to follow the procedures outlined in the protocol or inability to provide written informed consent
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
United States20 sites
GSK Investigational Site
Anaheim, California, 92801
GSK Investigational Site
Anniston, Alabama, 36207
GSK Investigational Site
Austin, Texas, 78704
GSK Investigational Site
Beverly Hills, California, 90211
GSK Investigational Site
Boise, Idaho, 83704
GSK Investigational Site
Cleveland, Ohio, 44122
GSK Investigational Site
Coral Gables, Florida, 33134
GSK Investigational Site
Fargo, North Dakota, 58103
GSK Investigational Site
Glendale, Arizona, 85308
GSK Investigational Site
Hackensack, New Jersey, 07601
GSK Investigational Site
Houston, Texas, 77081
GSK Investigational Site
Indianapolis, Indiana, 46260
GSK Investigational Site
Las Vegas, Nevada, 89119
GSK Investigational Site
Long Beach, California, 90806
GSK Investigational Site
Miami, Florida, 33169
GSK Investigational Site
Oklahoma City, Oklahoma, 73132
GSK Investigational Site
Portland, Oregon, 97239
GSK Investigational Site
San Antonio, Texas, 78229
GSK Investigational Site
Sarasota, Florida, 34239
GSK Investigational Site
West Palm Beach, Florida, 33409
About this study
Official title: A Study to Evaluate the Potential Incidence of Orthostatic Hypotension in Elderly Hypertensive Patients Following Administration of a Combination of COREG CR and Lisinopril
This is a multi-center, double-blind, randomized, placebo-controlled, 2-session crossover study to evaluate the incidence of orthostatic hypotension in elderly hypertensive subjects following co-administration of carvedilol CR and lisinopril.
- Conditions
- Hypertension
- Being tested
- Carvedilol CR capsules, Placebo, Lisinopril
- Keywords
- lisinopril, carvedilol, hypertension
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carvedilol CR capsulesDrug
The carvedilol micropump (COREG) CR cpsules will be available with doses of 20 milligrams and 40 milligrams administered orally once daily.
PlaceboDrug
Placebo capsules to match each dose level will be provided.
LisinoprilDrug
Lisinopril will be available as 10 milligrams tablets administered orally once daily.
| Study group | Role | What they receive |
|---|---|---|
| Subjects receiving treatment sequence AB | Experimental | Eligible subjects will receive treatment sequence AB; A= Placebo to match COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). Placebo to match COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14). B=COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14). Receives: Drug: Carvedilol CR capsules; Drug: Placebo; Drug: Lisinopril |
| Subjects receiving treatment sequence BA | Experimental | Eligible subjects will receive treatment sequence BA; B=COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14). A= Placebo to match COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). Placebo to match COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14). Receives: Drug: Carvedilol CR capsules; Drug: Placebo; Drug: Lisinopril |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of orthostasis 6 hours post dose on day 1, 7, 8, 14 in each dosing session
Measured: 6 hours post dose on day 1, 7, 8, 14 in each dosing session
To evaluate the incidence of orthostatic hypotension (defined as a decrease in SBP of ≥20 mmHg and/or a decrease in DBP of ≥10 mmHg in changing from the supine to the standing position) following co-administration of COREG CR and lisinopril
Measured: Up to Day 14
Secondary outcomes (5)
Relationship of concentration of drug to events 6 hours post dose on day 1, 7, 8, 14 in each dosing session
Measured: 6 hours post dose on day 1, 7, 8, 14 in each dosing session
Relationship of concentration of drug to events
Measured: 6 hours post dose on day 1, 7, 8, 14 in each dosing session
To evaluate the safety and tolerability of the co-administration of COREG CR and lisinopril
Measured: Up to Day 24
To evaluate the relationship between the plasma concentrations of carvedilol and lisinopril and the occurrence of orthostatic hypotension following co-administration of COREG CR and lisinopril
Measured: 6 hours post dose on day 1, 7, 8, 14 in each dosing session
To evaluate the effects of COREG CR on plasma renin activity
Measured: Up to Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2007 (estimated)
- Study start25 Sep 2007
- Primary completion3 Jun 2008
- Study completion3 Jun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Enrolment
- 62 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
- NCT00508365
- Sponsor's protocol ID
- CFD109701
- Status last verified
- Aug 2017
- First submitted
- 26 Jul 2007
- Last updated
- 9 Aug 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.
Publications
GSK has submitted manuscripts of these study results to peer-reviewed scientific journals which were not accepted for publication. GSK is providing the attached study results summary with a conclusion.
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Evaluate the Potential Incidence of Orthostatic Hypotension in Elderly Hypertensive Patients Following Administration of a Combination of COREG CR and Lisinopril
- ClinicalTrials.gov ID
- NCT00508365
- Acronym / sponsor ID
- CFD109701
- Conditions
- Hypertension
- Keywords
- lisinopril, carvedilol, hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 25 Sep 2007 (actual)
- Primary completion
- 3 Jun 2008 (actual)
- Study completion
- 3 Jun 2008 (actual)
- First posted
- 30 Jul 2007 (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 multi-center, double-blind, randomized, placebo-controlled, 2-session crossover study to evaluate the incidence of orthostatic hypotension in elderly hypertensive subjects following co-administration of carvedilol CR and lisinopril.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Subjects receiving treatment sequence AB | Experimental | Drug: Carvedilol CR capsules, Drug: Placebo, Drug: LisinoprilEligible subjects will receive treatment sequence AB; A= Placebo to match COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). Placebo to match COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14). B=COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14). |
| Subjects receiving treatment sequence BA | Experimental | Drug: Carvedilol CR capsules, Drug: Placebo, Drug: LisinoprilEligible subjects will receive treatment sequence BA; B=COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14). A= Placebo to match COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). Placebo to match COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14). |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- Males or females who are ≥ 65 years of age
- Body mass index (BMI) between 24 and 37 kg/m2 where: BMI = (weight in kg)/ (height in meters)2
- Subjects must have a documented history of essential hypertension and must be stable on treatment with an ACE inhibitor or angiotensin II receptor antagonist or renin antagonist and no more than one other antihypertensive medication at least 3 months before screening with a sitting SBP<180 mmHg and DBP<110 mmHg.
- All subjects must be able to be safely (in the opinion of the Investigator) withdrawn or down-titrated from all antihypertensive treatment(s) and transitioned to lisinopril 10 mg OD for the two-week run-in phase.
Key exclusion criteria (42 listed)
- Any clinically relevant abnormality identified on the screening history, physical or laboratory examination, or any other medical condition or circumstance making the volunteer unsuitable for participation in the study
- Subject who metabolizes carvedilol poorly based on CYP2D6 genotype as determined at screening
- Subject has persistent hyperkalemia or history of hyperkalemia resulting from either Type IV RTA (renal tubular acidosis) or previous treatment with an ACE inhibitor, ARB or renin inhibitor.
- Subject has malignant (accelerated) hypertension, history of malignant hypertension, or history of secondary forms of hypertension
- Subject has advanced hypertensive retinopathy (Keith Wagner Grade IV)
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 |
|---|---|---|
| Carvedilol CR capsulesThe carvedilol micropump (COREG) CR cpsules will be available with doses of 20 milligrams and 40 milligrams administered orally once daily. | Drug | Subjects receiving treatment sequence AB, Subjects receiving treatment sequence BA |
| PlaceboPlacebo capsules to match each dose level will be provided. | Drug | Subjects receiving treatment sequence AB, Subjects receiving treatment sequence BA |
| LisinoprilLisinopril will be available as 10 milligrams tablets administered orally once daily. | Drug | Subjects receiving treatment sequence AB, Subjects receiving treatment sequence BA |
Primary outcome
Assessment of orthostasis 6 hours post dose on day 1, 7, 8, 14 in each dosing session
Time frame: 6 hours post dose on day 1, 7, 8, 14 in each dosing session
To evaluate the incidence of orthostatic hypotension (defined as a decrease in SBP of ≥20 mmHg and/or a decrease in DBP of ≥10 mmHg in changing from the supine to the standing position) following co-administration of COREG CR and lisinopril
Time frame: Up to Day 14
5 secondary outcomes
Relationship of concentration of drug to events 6 hours post dose on day 1, 7, 8, 14 in each dosing session
Time frame: 6 hours post dose on day 1, 7, 8, 14 in each dosing session
Relationship of concentration of drug to events
Time frame: 6 hours post dose on day 1, 7, 8, 14 in each dosing session
To evaluate the safety and tolerability of the co-administration of COREG CR and lisinopril
Time frame: Up to Day 24
To evaluate the relationship between the plasma concentrations of carvedilol and lisinopril and the occurrence of orthostatic hypotension following co-administration of COREG CR and lisinopril
Time frame: 6 hours post dose on day 1, 7, 8, 14 in each dosing session
To evaluate the effects of COREG CR on plasma renin activity
Time frame: Up to Day 14
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 9 Aug 2017.
- BackgroundGSK has submitted manuscripts of these study results to peer-reviewed scientific journals which were not accepted for publication. GSK is providing the attached study results summary with a conclusion.
- Results for study CFD109701 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- 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.
- 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
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Carvedilol CR capsules and Lisinopril in people with Hypertension, run by GlaxoSmithKline at 20 sites in United States.
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 4 inclusion and 42 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 9 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States. 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?
Assessment of orthostasis 6 hours post dose on day 1, 7, 8, 14 in each dosing session (time frame: 6 hours post dose on day 1, 7, 8, 14 in each dosing session). 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?
On the ClinicalTrials.gov record for NCT00508365, which also lists 1 linked publication.
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 9 Aug 2017.