HypertensionPhase 1NCT01130168

The Effects of Antihypertensive Agents on Central Blood Pressure in Healthy Participants and Participants With Hypertension (MK-0000-166) (COMPLETED)

A Phase 1 study testing Comparator: Amlodipine and Comparator: ISMN ER in people with Hypertension, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will test the relationship between CBP (central blood pressure) and PBP (peripheral blood pressure) effects after single and multiple doses of Isosorbide mononitrate extended release (ISMN ER) or Amlodipine besylate in participants with hypertension. Read more about this study

Who is it for?: Ages 30 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Hypertension
What is being tested?: Comparator: Amlodipine and Comparator: ISMN ER
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 38 participants
Where: No sites listed yet
Study dates: May 2010to Nov 2010
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 30 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Participant is a male or female between 30 and 65 years of age (inclusive) at the pre-study (screening)
Female participant of childbearing potential must have a negative pregnancy test
Participant has a brachial systolic blood pressure >130 mm Hg
and <180 mm Hg
Participant has a Body Mass Index (BMI) that is >20 kg/m^2 and <35 kg/m^2
Participant has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months

Who cannot join

Female Participant is pregnant or lactating
Participant anticipates the use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) other than acetaminophen
Participant is currently a user (including "recreational use") of any illicit drugs, has a history of drug or alcohol abuse within approximately 2 years, or has a positive prestudy urine drug screen
Participant has a condition for which there is a warning, contraindication, or precaution against the use of ISMN ER including: acute myocardial infarction or congestive heart failure, hypotension, volume depletion, and pregnancy
Participant has a history of significant drug allergy or any clinically significant adverse experience of a serious nature related to the administration of either a marketed or an investigational drug, including nitrates, nitrites, Amlodipine, and ISMN ER

About this study

Official title: A Double-Blind, Randomized, Placebo-Controlled, 3-Period, Crossover Study to Evaluate the Effects of Antihypertensive Agents on Central Blood Pressure in Healthy Subjects and Patients With Hypertension

Conditions: Hypertension
Being tested: Placebo, Comparator: Amlodipine, Comparator: ISMN ER
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Placebo, capsule taken orally once daily during 4 weeks of treatment
Comparator: AmlodipineDrug
Amlodipine 10 mg, taken orally as two 5 mg capsules, single daily dose for 4 weeks
Comparator: ISMN ERDrug
ISMN ER 30 mg capsule, taken orally as single daily dose for 4 weeks

Study groups in NCT01130168
Study group	Role	What they receive
Placebo/ISMN ER/Amlodipine (Sequence 1)	Experimental	Participants received a dose-matched Placebo capsule orally for 4 weeks during Period 1, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 2, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 3, with a 2-week washout between each period. Receives: Drug: Placebo; Drug: Comparator: Amlodipine; Drug: Comparator: ISMN ER
ISMN ER/Amlodipine/Placebo (Sequence 2)	Experimental	Participants received a ISMN ER 30 mg capsule orally for 4 weeks during Period 1, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 2, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 3, with a 2-week washout between each period. Receives: Drug: Placebo; Drug: Comparator: Amlodipine; Drug: Comparator: ISMN ER
Amlodipine/Placebo/ISMN ER (Sequence 3)	Experimental	Participants received Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 1, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 2, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 3, with a 2-week washout between each period. Receives: Drug: Placebo; Drug: Comparator: Amlodipine; Drug: Comparator: ISMN ER
ISMN ER/Placebo/Amlodipine (Sequence 4)	Experimental	Participants received a ISMN ER 30 mg capsule orally for 4 weeks during Period 1, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 2, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 3, with a 2-week washout between each period. Receives: Drug: Placebo; Drug: Comparator: Amlodipine; Drug: Comparator: ISMN ER
Placebo/Amlodipine/ISMN ER (Sequence 5)	Experimental	Participants received a dose-matched Placebo capsule orally for 4 weeks during Period 1, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 2, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 3, with a 2-week washout between each period. Receives: Drug: Placebo; Drug: Comparator: Amlodipine; Drug: Comparator: ISMN ER
Amlodipine/ISMN ER/Placebo (Sequence 6)	Experimental	Participants received Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 1, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 2, followed by a dose-matched Placebo capsule for 4 weeks during Period, with a 2-week washout between each period. Receives: Drug: Placebo; Drug: Comparator: Amlodipine; Drug: Comparator: ISMN ER

What is being measured

The primary outcome is the main question the study is designed to answer.

Time-weighted Average (TWA) Change From Baseline (0 Hours) to 12 Hours in Heart-Rate-Corrected Augmentation Index (AIx) After A Single Dose of Treatment
The augmentation index (AIx) is a measure of systemic arterial stiffness, and is the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Single dose effects on AIx were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows:
HR-corrected AIx = -0.39 x (75 - HR) + AIx. This value was used for all AIx analyses.
Measured: Baseline (0 hrs), 12 hours post-dose (Day 1)
Change From Baseline (0 Hours) to Week 4 in Heart-Rate-Corrected AIx After Multiple Doses of Treatment
The augmentation index (AIx) is a measure of systemic arterial stiffness, and is the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows:
HR-corrected AIx = -0.39 x (75 - HR) + AIx. This value was used for all AIx analyses.
Measured: Baseline (0 hrs), 24 hours after the Day 28 dose
TWA Change From Baseline (0 Hours) to 12 Hours in Central Systolic Blood Pressure (SBP) After A Single Dose of Treatment
Central SBP was measured by the SphygmoCor® device. Single dose effects on central SBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
Measured: Baseline (0 hrs), 12 hours post-dose (Day 1)
Change From Baseline (0 Hours) to Week 4 in Central SBP After Multiple Doses of Treatment
Central SBP was measured by the SphygmoCor® device. Central SBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
Measured: Baseline (0 hrs), 24 hours after the Day 28 dose
TWA Change From Baseline (0 Hours) to 12 Hours in Central Diastolic Blood Pressure (DBP) After A Single Dose of Treatment
Central DBP was measured by the SphygmoCor® device. Single dose effects on central DBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
Measured: Baseline (0 hrs), 12 hours post-dose (Day 1)
Change From Baseline (0 Hours) to Week 4 in Central DBP After Multiple Doses of Treatment
Central DBP was measured by the SphygmoCor® device. Central DBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
Measured: Baseline (0 hrs), 24 hours after the Day 28 dose
TWA Change From Baseline (0 Hours) to 12 Hours in Peripheral SBP After A Single Dose of Treatment
Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Single dose effects on peripheral SBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
Measured: Baseline (0 hrs), 12 hours post-dose (Day 1)
Change From Baseline (0 Hours) to Week 4 in Peripheral SBP After Multiple Doses of Treatment
Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Peripheral SBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
Measured: Baseline (0 hrs), 24 hours after the Day 28 dose
TWA Change From Baseline (0 Hours) to 12 Hours in Peripheral DBP After A Single Dose of Treatment
Peripheral DBP was measured by Brachial Sphygmomanometer (standard cuff). Single dose effects on peripheral DBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
Measured: Baseline (0 hrs), 12 hours post-dose (Day 1)
Change From Baseline (0 Hours) to Week 4 in Peripheral DBP After Multiple Doses of Treatment
Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Peripheral DBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
Measured: Baseline (0 hrs), 24 hours after the Day 28 dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2010Nov 2010

First posted25 May 2010 (estimated)
Study startMay 2010
Primary completionNov 2010
Study completionNov 2010

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 Merck Sharp & Dohme LLCThe 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: Double blind
Who is masked: Participant, Investigator
Enrolment: 38 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01130168
Sponsor's protocol ID: 0000-166
Other IDs: 2010_537
Status last verified: Oct 2015
First submitted: 19 May 2010
Last updated: 9 Oct 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-Blind, Randomized, Placebo-Controlled, 3-Period, Crossover Study to Evaluate the Effects of Antihypertensive Agents on Central Blood Pressure in Healthy Subjects and Patients With Hypertension
ClinicalTrials.gov ID: NCT01130168
Acronym / sponsor ID: 0000-166
Conditions: Hypertension
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 38 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: May 2010
Primary completion: Nov 2010 (actual)
Study completion: Nov 2010 (actual)
First posted: 25 May 2010 (estimated)
Results: Posted 28 May 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 6

Arm	Type	Receives
Placebo/ISMN ER/Amlodipine (Sequence 1)	Experimental	Drug: Placebo, Drug: Comparator: Amlodipine, Drug: Comparator: ISMN ERParticipants received a dose-matched Placebo capsule orally for 4 weeks during Period 1, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 2, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 3, with a 2-week washout between each period.
ISMN ER/Amlodipine/Placebo (Sequence 2)	Experimental	Drug: Placebo, Drug: Comparator: Amlodipine, Drug: Comparator: ISMN ERParticipants received a ISMN ER 30 mg capsule orally for 4 weeks during Period 1, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 2, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 3, with a 2-week washout between each period.
Amlodipine/Placebo/ISMN ER (Sequence 3)	Experimental	Drug: Placebo, Drug: Comparator: Amlodipine, Drug: Comparator: ISMN ERParticipants received Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 1, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 2, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 3, with a 2-week washout between each period.
ISMN ER/Placebo/Amlodipine (Sequence 4)	Experimental	Drug: Placebo, Drug: Comparator: Amlodipine, Drug: Comparator: ISMN ERParticipants received a ISMN ER 30 mg capsule orally for 4 weeks during Period 1, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 2, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 3, with a 2-week washout between each period.
Placebo/Amlodipine/ISMN ER (Sequence 5)	Experimental	Drug: Placebo, Drug: Comparator: Amlodipine, Drug: Comparator: ISMN ERParticipants received a dose-matched Placebo capsule orally for 4 weeks during Period 1, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 2, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 3, with a 2-week washout between each period.
Amlodipine/ISMN ER/Placebo (Sequence 6)	Experimental	Drug: Placebo, Drug: Comparator: Amlodipine, Drug: Comparator: ISMN ERParticipants received Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 1, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 2, followed by a dose-matched Placebo capsule for 4 weeks during Period, with a 2-week washout between each period.

Who may qualify

Ages: 30 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Participant is a male or female between 30 and 65 years of age (inclusive) at the pre-study (screening)
Female participant of childbearing potential must have a negative pregnancy test
Participant has a brachial systolic blood pressure >130 mm Hg
and <180 mm Hg
Participant has a Body Mass Index (BMI) that is >20 kg/m^2 and <35 kg/m^2

Key exclusion criteria (5 listed)

Female Participant is pregnant or lactating
Participant anticipates the use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) other than acetaminophen
Participant is currently a user (including "recreational use") of any illicit drugs, has a history of drug or alcohol abuse within approximately 2 years, or has a positive prestudy urine drug screen
Participant has a condition for which there is a warning, contraindication, or precaution against the use of ISMN ER including: acute myocardial infarction or congestive heart failure, hypotension, volume depletion, and pregnancy
Participant has a history of significant drug allergy or any clinically significant adverse experience of a serious nature related to the administration of either a marketed or an investigational drug, including nitrates, nitrites, Amlodipine, and ISMN ER

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
PlaceboPlacebo, capsule taken orally once daily during 4 weeks of treatment	Drug	Amlodipine/ISMN ER/Placebo (Sequence 6), Amlodipine/Placebo/ISMN ER (Sequence 3), ISMN ER/Amlodipine/Placebo (Sequence 2), ISMN ER/Placebo/Amlodipine (Sequence 4), Placebo/Amlodipine/ISMN ER (Sequence 5), Placebo/ISMN ER/Amlodipine (Sequence 1)
Comparator: AmlodipineAmlodipine 10 mg, taken orally as two 5 mg capsules, single daily dose for 4 weeks	Drug	Amlodipine/ISMN ER/Placebo (Sequence 6), Amlodipine/Placebo/ISMN ER (Sequence 3), ISMN ER/Amlodipine/Placebo (Sequence 2), ISMN ER/Placebo/Amlodipine (Sequence 4), Placebo/Amlodipine/ISMN ER (Sequence 5), Placebo/ISMN ER/Amlodipine (Sequence 1)
Comparator: ISMN ERISMN ER 30 mg capsule, taken orally as single daily dose for 4 weeks	Drug	Amlodipine/ISMN ER/Placebo (Sequence 6), Amlodipine/Placebo/ISMN ER (Sequence 3), ISMN ER/Amlodipine/Placebo (Sequence 2), ISMN ER/Placebo/Amlodipine (Sequence 4), Placebo/Amlodipine/ISMN ER (Sequence 5), Placebo/ISMN ER/Amlodipine (Sequence 1)

Primary outcome

Time-weighted Average (TWA) Change From Baseline (0 Hours) to 12 Hours in Heart-Rate-Corrected Augmentation Index (AIx) After A Single Dose of Treatment
Time frame: Baseline (0 hrs), 12 hours post-dose (Day 1)
The augmentation index (AIx) is a measure of systemic arterial stiffness, and is the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Single dose effects on AIx were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. This value was used for all AIx analyses.
Change From Baseline (0 Hours) to Week 4 in Heart-Rate-Corrected AIx After Multiple Doses of Treatment
Time frame: Baseline (0 hrs), 24 hours after the Day 28 dose
The augmentation index (AIx) is a measure of systemic arterial stiffness, and is the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. This value was used for all AIx analyses.
TWA Change From Baseline (0 Hours) to 12 Hours in Central Systolic Blood Pressure (SBP) After A Single Dose of Treatment
Time frame: Baseline (0 hrs), 12 hours post-dose (Day 1)
Central SBP was measured by the SphygmoCor® device. Single dose effects on central SBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
Change From Baseline (0 Hours) to Week 4 in Central SBP After Multiple Doses of Treatment
Time frame: Baseline (0 hrs), 24 hours after the Day 28 dose
Central SBP was measured by the SphygmoCor® device. Central SBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
TWA Change From Baseline (0 Hours) to 12 Hours in Central Diastolic Blood Pressure (DBP) After A Single Dose of Treatment
Time frame: Baseline (0 hrs), 12 hours post-dose (Day 1)
Central DBP was measured by the SphygmoCor® device. Single dose effects on central DBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
Change From Baseline (0 Hours) to Week 4 in Central DBP After Multiple Doses of Treatment
Time frame: Baseline (0 hrs), 24 hours after the Day 28 dose
Central DBP was measured by the SphygmoCor® device. Central DBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
TWA Change From Baseline (0 Hours) to 12 Hours in Peripheral SBP After A Single Dose of Treatment
Time frame: Baseline (0 hrs), 12 hours post-dose (Day 1)
Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Single dose effects on peripheral SBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
Change From Baseline (0 Hours) to Week 4 in Peripheral SBP After Multiple Doses of Treatment
Time frame: Baseline (0 hrs), 24 hours after the Day 28 dose
Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Peripheral SBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
TWA Change From Baseline (0 Hours) to 12 Hours in Peripheral DBP After A Single Dose of Treatment
Time frame: Baseline (0 hrs), 12 hours post-dose (Day 1)
Peripheral DBP was measured by Brachial Sphygmomanometer (standard cuff). Single dose effects on peripheral DBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
Change From Baseline (0 Hours) to Week 4 in Peripheral DBP After Multiple Doses of Treatment
Time frame: Baseline (0 hrs), 24 hours after the Day 28 dose
Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Peripheral DBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.

Results and safety

Results posted to the registry on 28 May 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo/ISMN ER/Amlodipine (Sequence 1)	6	6
ISMN ER/Amlodipine/Placebo (Sequence 2)	7	6
Amlodipine/Placebo/ISMN ER (Sequence 3)	6	5
ISMN ER/Placebo/Amlodipine (Sequence 4)	8	5
Placebo/Amlodipine/ISMN ER (Sequence 5)	5	5
Amlodipine/ISMN ER/Placebo (Sequence 6)	6	6

Primary outcome: Time-weighted Average (TWA) Change From Baseline (0 Hours) to 12 Hours in Heart-Rate-Corrected Augmentation Index (AIx) After A Single Dose of Treatment

Time frame: Baseline (0 hrs), 12 hours post-dose (Day 1). Least squares mean (Standard Deviation). Unit: percent

Measure	ISMN ER n = 32	Amlodipine n = 33	Placebo n = 33
Value	-11.1 (4.5)	-0.7 (4.5)	2.1 (4.5)

ISMN ER vs Placebo: Mean Difference (Final Values): -13.1 (95% CI -15.3 to -10.9), p <0.0005, ANOVA
Amlodipine vs Placebo: Mean Difference (Final Values): -2.7 (95% CI -4.9 to -0.6), p = 0.016, ANOVA

Population analysed: 33 participants completed all study periods and provided more than 1 period of BP data, and were thus evaluable for the BP analyses. Unreliable SphygmoCor® data were collected for one participant in the ISM ER treatment group, therefore this participant was excluded from the single dose AIx analysis.

Primary outcome: Change From Baseline (0 Hours) to Week 4 in Heart-Rate-Corrected AIx After Multiple Doses of Treatment

Time frame: Baseline (0 hrs), 24 hours after the Day 28 dose. Least squares mean (Standard Deviation). Unit: percent

Measure	ISMN ER n = 31	Amlodipine n = 33	Placebo n = 33
Value	2.5 (6.2)	-4.7 (6.2)	1.2 (6.2)

ISMN ER vs Placebo: Mean Difference (Final Values): 1.3 (95% CI -1.7 to 4.3), p = 0.407, ANOVA
Amlodipine vs Placebo: Mean Difference (Final Values): -5.9 (95% CI -8.9 to -2.9), p <0.0005, ANOVA

Population analysed: 33 participants completed all study periods and provided more than 1 period of BP data, and were thus evaluable for the BP analyses. Unreliable SphygmoCor® data were collected for two participants in the ISM ER treatment group, therefore these participants were excluded from the multiple dose AIx analysis.

Primary outcome: TWA Change From Baseline (0 Hours) to 12 Hours in Central Systolic Blood Pressure (SBP) After A Single Dose of Treatment

Time frame: Baseline (0 hrs), 12 hours post-dose (Day 1). Least squares mean (Standard Deviation). Unit: mm mercury (Hg)

Measure	ISMN ER n = 32	Amlodipine n = 33	Placebo n = 33
Value	-14.7 (7.7)	-3.6 (7.7)	2.7 (7.7)

ISMN ER vs Placebo: Mean Difference (Final Values): -17.4 (95% CI -21.2 to -10.1), p <0.0005, ANOVA
Amlodipine vs Placebo: Mean Difference (Final Values): -6.3 (95% CI -17.4 to -6.3), p = 0.001, ANOVA

Primary outcome: Change From Baseline (0 Hours) to Week 4 in Central SBP After Multiple Doses of Treatment

Time frame: Baseline (0 hrs), 24 hours after the Day 28 dose. Least squares mean (Standard Deviation). Unit: mm mercury (Hg)

Measure	ISMN ER n = 32	Amlodipine n = 33	Placebo n = 33
Value	-0.7 (11.6)	-12.9 (11.6)	3.2 (11.6)

ISMN ER vs Placebo: Mean Difference (Final Values): -3.8 (95% CI -9.5 to 1.8), p = 0.186, ANOVA
Amlodipine vs Placebo: Mean Difference (Final Values): -16.1 (95% CI -21.7 to -10.5), p <0.0005, ANOVA

Adverse events

Other adverse events reported at 5.0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 34 (0%)	7 of 34 (20.6%)	Not reported
ISMN ER	0 of 38 (0%)	18 of 38 (47.4%)	Not reported
Amlodipine	0 of 37 (0%)	9 of 37 (24.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Medical Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Comparator: Amlodipine and Comparator: ISMN ER in people with Hypertension, run by Merck Sharp & Dohme LLC.

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 6 inclusion and 5 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 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

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 28 May 2012). 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?

Time-weighted Average (TWA) Change From Baseline (0 Hours) to 12 Hours in Heart-Rate-Corrected Augmentation Index (AIx) After A Single Dose of Treatment (time frame: Baseline (0 hrs), 12 hours post-dose (Day 1)). The study lists 10 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 NCT01130168.

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 Oct 2015.