Open-Label Long-Term Safety and Efficacy Study of Fixed Dose Combination of Nifedipine Gastrointestinal Therapeutic System and Candesartan Cilexetil in Subjects With Moderate to Severe Essential Hypertension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01788358
First received: February 7, 2013
Last updated: August 19, 2015
Last verified: August 2015

February 7, 2013
August 19, 2015
February 2013
May 2014   (final data collection date for primary outcome measure)
  • Number of Subjects With All Treatment-emergent Adverse Events (TEAEs) and Drug-related TEAEs up to Week 28 [ Time Frame: From the time of first study drug administration up to Week 28 ] [ Designated as safety issue: Yes ]
    An adverse event (AE) is any untoward medical occurrence (that is, any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication.
  • Number of Subjects With Treatment-emergent Adverse Events (TEAEs) of Special Interest up to Week 28 [ Time Frame: From the time of first study drug administration up to Week 28 ] [ Designated as safety issue: Yes ]
    An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication. TEAEs of special interest included the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as oedema, headache, and flushing). Only subjects who had TEAEs of special interest as mild, moderate or severe were reported.
  • Number of Subjects With All Treatment-emergent Adverse Events (TEAEs) and Drug-related TEAEs up to Week 52/End of Study (EOS) [ Time Frame: From the time of first study drug administration up to Week 52/EOS ] [ Designated as safety issue: Yes ]
    An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication.
  • Number of Subjects With Treatment-emergent Adverse Events (TEAEs) of Special Interest up to Week 52/End of Study (EOS) [ Time Frame: From the time of study treatment up to Week 52/EOS ] [ Designated as safety issue: Yes ]
    An AE is any untoward medical occurrence (that is, any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. AEs were considered to be treatment-emergent if they had started or worsened after first application of study medication. TEAEs of special interest included the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as oedema, headache, and flushing). Only subjects who had TEAEs of special interest as mild, moderate or severe were reported.
  • The long-term safety and tolerability of once daily Nifedipine/Candesartan (BAY98-7106) [ Time Frame: During treatment period lasting 28 weeks ] [ Designated as safety issue: Yes ]
    The primary outcome is evaluated by incidence of all treatment-emergent adverse events; incidence of drug-related treatment-emergent adverse events; adverse events of special interest - including the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as peripheral edema, headache, and flushing) will be a particular focus.
  • The long-term safety and tolerability of once daily Nifedipine/Candesartan (BAY98-7106) [ Time Frame: During treatment period lasting 52 weeks ] [ Designated as safety issue: Yes ]
    The primary outcome is evaluated by incidence of all treatment-emergent adverse events; incidence of drug-related treatment-emergent adverse events; adverse events of special interest - including the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as peripheral edema, headache, and flushing) will be a particular focus.
Complete list of historical versions of study NCT01788358 on ClinicalTrials.gov Archive Site
  • Number of Subjects With Clinically Relevant Changes in Laboratory Parameters [ Time Frame: Baseline (Week 0) up to Week 52/EOS ] [ Designated as safety issue: Yes ]
    Laboratory evaluations of blood and urine samples were performed, including hematology (hematocrit, hemoglobin, red blood cells count, white blood cells count, neutrophils, lymphocytes, monocytes, eosinophils, basophils, platelets), blood chemistry (sodium, potassium, chloride, bicarbonate, uric acid, total protein, albumin, calcium, blood urea nitrogen, creatinine, aspartate transaminase, alanine transaminase, lactate dehydrogenase, gamma glutamyl transferase, alkaline phosphatase, creatine kinase, total bilirubin, direct bilirubin, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, fasting glucose), urinalysis (pH, blood, specific gravity, glucose, protein, cells/sediment). A laboratory test abnormality considered clinically relevant, for example, causing withdrawal by subject, requiring treatment or causing apparent clinical manifestations, or judged relevant by the investigator, were reported as AEs.
  • Change From Baseline In Mean Seated Systolic Blood Pressure (MSSBP) At Weeks 28 And 52 [ Time Frame: Baseline (Week 0), Weeks 28 and 52 ] [ Designated as safety issue: No ]
  • Change From Baseline in Mean Seated Diastolic Blood Pressure (MSDBP) at Weeks 28 and 52 [ Time Frame: Baseline (Week 0), Weeks 28 and 52 ] [ Designated as safety issue: No ]
  • Blood Pressure Control Rate at Weeks 28 and 52 [ Time Frame: Weeks 28 and 52 ] [ Designated as safety issue: No ]
    Control rate was defined as the percentage of subjects that reached a predetermined blood pressure (BP) target of BP less than (<) 140/90 mmHg.
  • Blood Pressure Response Rate at Weeks 28 and 52 [ Time Frame: Weeks 28 and 52 ] [ Designated as safety issue: No ]
    Response rate was defined as the percentage of subjects who achieved a systolic blood pressure response (MSSBP of <140 mmHg or a reduction of MSSBP of more than (>) 20 mmHg from baseline value), or a diastolic blood pressure response (MSDBP of <90 mmHg or a reduction of MSDBP of >10 mmHg from baseline value).
  • Change in mean seated systolic blood pressure (MSSBP) [ Time Frame: From baseline to week 28 ] [ Designated as safety issue: No ]
  • Change in mean seated systolic blood pressure (MSSBP) [ Time Frame: From baseline to week 52 ] [ Designated as safety issue: No ]
  • Change in mean seated diastolic blood pressure(MSDBP) [ Time Frame: From baseline to week 28 ] [ Designated as safety issue: No ]
  • Change in mean seated diastolic blood pressure(MSDBP) [ Time Frame: From baseline to week 52 ] [ Designated as safety issue: No ]
  • Blood pressure Response Rate [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    Response rate is defined as the percentage of subjects achieving a systolic blood pressure (SBP) response (MSSBP of < 140 mmHg or a reduction of MSSBP of > 20 mmHg from baseline value), or a diastolic blood pressure (DBP) response (i.e. MSDBP of < 90 mmHg or a reduction of MSDBP of > 10 mmHg from baseline value).
  • Blood pressure Response Rate [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Response rate is defined as the percentage of subjects achieving a systolic blood pressure (SBP) response (MSSBP of < 140 mmHg or a reduction of MSSBP of > 20 mmHg from baseline value), or a diastolic blood pressure (DBP) response (i.e. MSDBP of < 90 mmHg or a reduction of MSDBP of > 10 mmHg from baseline value).
  • Blood pressure Control Rate [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    Control rate is the percentage of subjects that reach the predetermined blood pressure (BP) target < 140/90 mmHg. In addition, the percentage of subjects that reach the predetermined BP target will be provided as well (BP < 140/90 mmHg for subjects without diabetes and chronic renal disorder, and BP <130/80 mmHg for subjects with diabetes or chronic renal disorder).
  • Blood pressure Control Rate [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Control rate is the percentage of subjects that reach the predetermined blood pressure (BP) target < 140/90 mmHg. In addition, the percentage of subjects that reach the predetermined BP target will be provided as well (BP < 140/90 mmHg for subjects without diabetes and chronic renal disorder, and BP <130/80 mmHg for subjects with diabetes or chronic renal disorder).
Not Provided
Not Provided
 
Open-Label Long-Term Safety and Efficacy Study of Fixed Dose Combination of Nifedipine Gastrointestinal Therapeutic System and Candesartan Cilexetil in Subjects With Moderate to Severe Essential Hypertension
Multicenter, Open-Label, Long-Term Safety and Efficacy Study of the Fixed Dose Combination of Nifedipine Gastrointestinal Therapeutic System and Candesartan Cilexetil in Adult Subjects With Moderate to Severe Essential Hypertension

This study examines the long term safety and efficacy of the Fixed Dose combination BAY98-7106 (nifedipine plus candesartan primarily at the highest dose in development) in patients with moderate to severe hypertension.

Patients meeting the entry criteria, will receive the Fixed Dose combination for 28 weeks, including 8 weeks with stepwise dose increase up to the high target dose. The first 200 subjects completing 28 weeks will continue treatment for additional 24 weeks (52 weeks in total).

Subjects who do not tolerate an increased dose will be treated at their highest tolerable dose.

Not Provided
Interventional
Phase 3
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Hypertension
  • Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
    Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 30/8 mg, orally once daily
  • Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
    Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 30/16 mg, orally once daily
  • Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
    Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 60/16 mg, orally once daily
  • Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
    Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106), tablet, 60/32 mg, orally once daily
Experimental: Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Subjects received nifedipine gastrointestinal therapeutic system (GITS) / candesartan cilexetil fixed dose combination (FDC) (BAY98-7106) tablet orally, once daily in the morning of Visit 1 (Week 0) for 28 or 52 weeks. The starting dose (30/8 milligram [mg] or 30/16 mg) was determined based on local practice and clinical judgment by the investigator. Based on the experience of symptomatic and asymptomatic hypotension, peripheral edema or significant tolerability, the doses were up-titrated to the highest target dose (60/32 mg).
Interventions:
  • Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
  • Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
  • Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
  • Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
508
May 2014
May 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Subjects must have moderate to severe essential hypertension (Grade 2 or Grade 3, WHO classifications). At Visit 1, subjects not treated with antihypertensive medications are to have Mean sitting systolic blood pressure (MSSBP) of >/= 160 mmHg and < 200 mmHg, as measured by a calibrated electronic BP measuring device. For other subjects who are treated with antihypertensive medication before, they should have MSSBP >/= 160 mmHg and <200 mmHg after wash out.
  • Women of childbearing potential and men must agree to use adequate contraception other than hormonal contraceptives when sexually active

Exclusion Criteria:

  • Mean seated systolic blood pressure >/= 200 mmHg and/or mean seated diastolic blood pressure >/= 120 mm/Hg
  • Mean seated diastolic blood pressure < 60 mm/Hg
  • Differences greater than 20 mmHg for systolic blood pressure and 10 mmHg for diastolic blood pressure are present on 3 consecutive blood pressure readings at visit 0
  • Any history of hypertensive emergency
  • Evidence of secondary hypertension such as coarctation of the aorta, pheochromocytoma, hyperaldosteronism, etc.
  • Cerebrovascular ischemic event (stroke, transient ischemic attack [TIA])within the previous 12 months
  • History of intracerebral hemorrhage or subarachnoid hemorrhage
  • History of hypertensive retinopathy - known Keith-Wagener Grade III or IV
  • Any history of heart failure, New York Heart Association (NYHA) classification III or IV
  • Severe coronary heart disease as manifest by a history of myocardial infarction or unstable angina in the last 6 months prior to visit 0
  • Type 1 diabetes mellitus (DM) or poorly controlled Type 2 DM as evidenced by HbA1C of greater than 9% on visit 0.
  • Hyperkalemia: potassium above the upper limit of normal in the laboratory range
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   Canada,   Germany,   Poland,   United Kingdom
 
NCT01788358
14801, 2012-004515-32
No
Bayer
Bayer
Not Provided
Study Director: Bayer Study Director Bayer
Bayer
August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP