Study of the Efficacy and Safety of LCZ696 Alone and in Combination With Amlodipine in Patients With Hypertension
4. august 2014 oppdatert av: Novartis Pharmaceuticals
An 8-week Randomized, Double-blind, Placebo-controlled Factorial Study to Evaluate the Efficacy and Safety of LCZ696 Alone and in Combination With Amlodipine in Patients With Essential Hypertension
To evaluate the blood pressure lowering effect and safety of LCZ696 when given alone and in combination with amlodipine in patients with essential hypertension.
Studieoversikt
Status
Tilbaketrukket
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Fase
- Fase 3
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- Male or female outpatients
- Patients with mild-to-moderate hypertension, untreated or currently taking antihypertensive therapy
- Treated patients (using antihypertensive treatments within 4 weeks prior to Visit 1) must have an msSBP ≥150 mmHg and <180 mmHg at the randomization visit and msSBP ≥140 mmHg <180 mmHg at the preceding visit.
- Untreated patients (newly diagnosed with essential hypertension or having a history of hypertension but have not been taking any antihypertensive drugs for at least 4 weeks prior to Visit 1) must have an msSBP ≥150 mmHg and <180 mmHg at both the randomization visit and the preceding visit.
- Patients must have an absolute difference of ≤15 mmHg in msSBP between the randomization visit and the preceding visit.
- Ability to communicate and comply with all study requirements and demonstrate good medication compliance (≥ 80% compliance rate) during the treatment run-in period.
Exclusion Criteria:
- Severe hypertension (msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg)
- History of angioedema, drug-related or otherwise
- History or evidence of a secondary form of hypertension, including but not limited to any of the following: renal parenchymal hypertension, renovascular hypertension (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced hypertension
- Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke
- History of myocardial infarction, coronary bypass surgery or any percutaneous coronary intervention (PCI) during the 12 months prior to Visit 1
- Pregnant or lactating women
- Women of child-bearing potential not using highly effective methods of contraception Other protocol defined inclusion/exclusion criteria may apply
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Dobbelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: LCZ696 200 mg
Patients randomized to this treatment arm will receive LCZ696 200 mg once daily for 8 weeks.
|
Experimental monotherapy doses
|
|
Eksperimentell: LCZ696 400 mg
Patients randomized to this treatment arm will receive LCZ696 400 mg once daily for 8 weeks.
|
Experimental monotherapy doses
|
|
Aktiv komparator: Amlodipine 5 mg
Patients randomized to this treatment arm will receive amlodipine 5 mg once daily for 8 weeks.
|
Active comparator monotherapy doses
|
|
Aktiv komparator: Amlodipine 10 mg
Patients randomized to this treatment arm will receive amlodipine 10 mg once daily for 8 weeks.
|
Active comparator monotherapy doses
|
|
Eksperimentell: LCZ696 200 mg and amlodipine 5 mg
Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 8 weeks.
|
Experimental combination doses
|
|
Eksperimentell: LCZ696 200 mg and amlodipine 10 mg
Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 1 week followed by LCZ696 200 mg and amlodipine 10 mg once daily for 7 weeks.
|
Experimental combination doses
|
|
Eksperimentell: LCZ696 400 mg and amlodipine 5 mg
Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 1 week followed by LCZ696 400 mg and amlodipine 5 mg once daily for 7 weeks.
|
Experimental combination doses
|
|
Eksperimentell: LCZ696 400 mg and amlodipine 10 mg
Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 1 week followed by LCZ696 400 mg and amlodipine 10 mg once daily for 7 weeks.
|
Experimental combination doses
|
|
Placebo komparator: Placebo
Patients randomized to this treatment arm will receive placebo once daily for 8 weeks.
|
Placebo comparator dose
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Change from baseline in mean sitting systolic blood pressure (msSBP) of LCZ696 monotherapy compared to placebo
Tidsramme: baseline, 8 weeks
|
Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits.
At the first study visit, blood pressure will be measured in both arms and the arm with highest sitting SBP will be found and used for all subsequent readings throughout the study.
The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting systolic blood pressure measurements will be used as the mean sitting systolic blood pressure for that visit.
|
baseline, 8 weeks
|
|
Change from baseline in mean sitting systolic blood pressure (msSBP) of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone.
Tidsramme: baseline, 8 weeks
|
Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits.
The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting systolic blood pressure measurements will be used as the mean sitting systolic blood pressure for that visit.
|
baseline, 8 weeks
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Change from baseline in mean sitting Diastolic Blood Pressure (msDBP) of LCZ696 monotherapy compared to placebo
Tidsramme: baseline, 8 weeks
|
Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits.
The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting diastolic blood pressure measurements will be used as the mean sitting diastolic blood pressure for that visit.
|
baseline, 8 weeks
|
|
Change from baseline in mean sitting Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
Tidsramme: baseline, 8 weeks
|
Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits.
The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting diastolic blood pressure measurements will be used as the mean sitting diastolic blood pressure for that visit.
|
baseline, 8 weeks
|
|
Change from baseline in pulse pressure
Tidsramme: baseline, 8 weeks
|
Pulse pressure will be calculated as the difference between msSBP and msDBP for both office BP and ABPM.
|
baseline, 8 weeks
|
|
Change from baseline in mean 24-hour ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo
Tidsramme: baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean 24-hour ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo
Tidsramme: baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo
Tidsramme: baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo
Tidsramme: baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo
Tidsramme: baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo
Tidsramme: baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in trough to peak ratio of mean 24-hour ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo
Tidsramme: baseline, 8 weeks
|
The trough to peak ratio of mean 24-hour ambulatory Systolic Blood Pressure will be calculated using the systolic blood pressure effects at trough (post-dosing hour 24) compared to the maximum systolic blood pressure effect found in the hours after dosing.
|
baseline, 8 weeks
|
|
Change from baseline in trough to peak ratio of mean 24-hour ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo
Tidsramme: baseline, 8 weeks
|
The trough to peak ratio of mean 24-hour ambulatory Diastolic Blood Pressure will be calculated using the diastolic blood pressure effects at trough (post-dosing hour 24) compared to the maximum diastolic blood pressure effect found in the hours after dosing.
|
baseline, 8 weeks
|
|
Change from baseline in mean 24-hour ambulatory Systolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
Tidsramme: baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean 24-hour ambulatory Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
Tidsramme: baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Systolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
Tidsramme: baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean daytime ( > 6am and ≤ 10 pm) ambulatory Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
Tidsramme: baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Systolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
Tidsramme: baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Change from baseline in mean nighttime (> 10 pm and ≤ 6 am) ambulatory Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone
Tidsramme: baseline, 8 weeks
|
The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.
|
baseline, 8 weeks
|
|
Percentage of patients achieving msSBP <140 mmHg and msDBP <90 mmHg
Tidsramme: 8 weeks
|
The percentage of patients achieving blood pressure control (msSBP <140 mmHg and msDBP <90 mmHg) after 8 weeks of treatment will be calculated.
|
8 weeks
|
|
Percentage of patients achieving msSBP <140 mmHg or a reduction ≥20 mmHg from baseline
Tidsramme: Baseline, 8 weeks
|
The percentage of patients achieving a successful response in msSBP (msSBP <140 mmHg or a reduction ≥20 mmHg from baseline) after 8 weeks of treatment will be calculated.
|
Baseline, 8 weeks
|
|
Percentage of patients achieving msDBP <90 mmHg or a reduction ≥10 mmHg from baseline
Tidsramme: Baseline, 8 weeks
|
The percentage of patients achieving a successful response in msSBP (msDBP <90 mmHg or a reduction ≥10 mmHg from baseline) after 8 weeks of treatment will be calculated.
|
Baseline, 8 weeks
|
|
Number of patients reporting adverse events
Tidsramme: 8 weeks
|
As an assessment of safety of monotherapy and combination therapy of LCZ696, total adverse events, serious adverse events and deaths after 8 weeks of treatment will be reported .
|
8 weeks
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. april 2014
Primær fullføring (Forventet)
1. april 2015
Studiet fullført (Forventet)
1. april 2015
Datoer for studieregistrering
Først innsendt
24. mai 2013
Først innsendt som oppfylte QC-kriteriene
24. mai 2013
Først lagt ut (Anslag)
30. mai 2013
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
5. august 2014
Siste oppdatering sendt inn som oppfylte QC-kriteriene
4. august 2014
Sist bekreftet
1. august 2014
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Kardiovaskulære sykdommer
- Vaskulære sykdommer
- Hypertensjon
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Antihypertensive midler
- Vasodilaterende midler
- Membrantransportmodulatorer
- Kalsiumregulerende hormoner og midler
- Kalsiumkanalblokkere
- Angiotensinreseptorantagonister
- Amlodipin
- Sacubitril og valsartan natriumhydrat medikamentkombinasjon
Andre studie-ID-numre
- CLCZ696A2320
- 2013-001643-30 (EudraCT-nummer)
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