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Trial record 43 of 143 for:    NIFEDIPINE

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

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ClinicalTrials.gov Identifier: NCT01788358
Recruitment Status : Completed
First Posted : February 11, 2013
Results First Posted : August 17, 2015
Last Update Posted : October 24, 2017
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hypertension
Intervention Drug: Nifedipine GITS/Candesartan Cilexetil FDC(BAY98-7106)
Enrollment 508
Recruitment Details The study was conducted at 70 study centers between 14 February 2013 (first subject first visit) and 1 May 2014 (last subject last visit).
Pre-assignment Details Of 753 subjects screened, 245 subjects were not enrolled, due to screen failure for 215 subjects, consent withdrawal by 23 subjects, protocol violation by 5 subjects, 1 subject was lost to follow-up and recruitment stopped for 1 subject. Remaining 508 subjects were enrolled and received at least 1 treatment with study drug.
Arm/Group Title Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Hide Arm/Group Description 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).
Period Title: Overall Study
Started 508
Treated 508
Completed Week 28 417
Entered Extension to Week 52 200 [1]
Completed Week 52 193
Completed 410 [2]
Not Completed 98
Reason Not Completed
Other             11
Logistical difficulties             1
Lost to Follow-up             5
Protocol Violation             3
Withdrawal by Subject             26
Lack of Efficacy             1
Adverse Event             51
[1]
Only the first 200 subjects who completed Week 28 visit, continued treatment up to 52 weeks.
[2]
217 subjects completed the study at Week 28 while the remaining 193 subjects completed at Week 52
Arm/Group Title Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Hide Arm/Group Description 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).
Overall Number of Baseline Participants 508
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 508 participants
59  (10.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 508 participants
Female
186
  36.6%
Male
322
  63.4%
Systolic blood pressure  
Mean (Standard Deviation)
Unit of measure:  Millimeter of mercury (mmHg)
Number Analyzed 508 participants
170.7  (8.9)
Diastolic blood pressure  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 508 participants
95.6  (10.4)
1.Primary Outcome
Title Number of Subjects With All Treatment-emergent Adverse Events (TEAEs) and Drug-related TEAEs up to Week 28
Hide Description 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.
Time Frame From the time of first study drug administration up to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (SAF): All the subjects enrolled into the open-label treatment period and took at least one unit of the study medication.
Arm/Group Title Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 508
Measure Type: Number
Unit of Measure: Subjects
All TEAEs 390
Drug-related TEAEs 230
2.Primary Outcome
Title Number of Subjects With Treatment-emergent Adverse Events (TEAEs) of Special Interest up to Week 28
Hide Description 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.
Time Frame From the time of first study drug administration up to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
SAF
Arm/Group Title Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 508
Measure Type: Number
Unit of Measure: Subjects
Oedema (mild) 124
Oedema (moderate) 54
Oedema (severe) 7
Headache (mild) 31
Headache (moderate) 15
Flushing (mild) 3
Symptomatic hypotension (mild) 4
3.Primary Outcome
Title Number of Subjects With All Treatment-emergent Adverse Events (TEAEs) and Drug-related TEAEs up to Week 52/End of Study (EOS)
Hide Description 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.
Time Frame From the time of first study drug administration up to Week 52/EOS
Hide Outcome Measure Data
Hide Analysis Population Description
SAF
Arm/Group Title Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 508
Measure Type: Number
Unit of Measure: Subjects
All TEAEs 404
Drug-related TEAEs 238
4.Primary Outcome
Title Number of Subjects With Treatment-emergent Adverse Events (TEAEs) of Special Interest up to Week 52/End of Study (EOS)
Hide Description 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.
Time Frame From the time of study treatment up to Week 52/EOS
Hide Outcome Measure Data
Hide Analysis Population Description
SAF
Arm/Group Title Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 508
Measure Type: Number
Unit of Measure: Subjects
Oedema (mild) 131
Oedema (moderate) 56
Oedema(severe) 7
Headache (mild) 31
Headache (moderate) 17
Flushing (mild) 3
Symptomatic hypotension (mild) 4
5.Secondary Outcome
Title Number of Subjects With Clinically Relevant Changes in Laboratory Parameters
Hide Description 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.
Time Frame Baseline (Week 0) up to Week 52/EOS
Hide Outcome Measure Data
Hide Analysis Population Description
SAF
Arm/Group Title Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 508
Measure Type: Number
Unit of Measure: Subjects
0
6.Secondary Outcome
Title Change From Baseline In Mean Seated Systolic Blood Pressure (MSSBP) At Weeks 28 And 52
Hide Description [Not Specified]
Time Frame Baseline (Week 0), Weeks 28 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intention-to-treat analysis set (mITT): All the subjects enrolled into the open-label treatment period and took at least one unit of the study medication.
Arm/Group Title Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 508
Mean (Standard Deviation)
Unit of Measure: millimeter of mercury (mmHg)
Baseline 170.7  (8.9)
Change at Week 28 -30.4  (17.7)
Change at Week 52 -30.1  (18.4)
7.Secondary Outcome
Title Change From Baseline in Mean Seated Diastolic Blood Pressure (MSDBP) at Weeks 28 and 52
Hide Description [Not Specified]
Time Frame Baseline (Week 0), Weeks 28 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 508
Mean (Standard Deviation)
Unit of Measure: millimeter of mercury (mmHg)
Baseline 95.6  (10.4)
Change at Week 28 -12.7  (10.6)
Change at Week 52 -12.8  (10.7)
8.Secondary Outcome
Title Blood Pressure Control Rate at Weeks 28 and 52
Hide Description Control rate was defined as the percentage of subjects that reached a predetermined blood pressure (BP) target of BP less than (<) 140/90 mmHg.
Time Frame Weeks 28 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 508
Measure Type: Number
Unit of Measure: percentage of subjects
Week 28 51.4
Week 52 51.6
9.Secondary Outcome
Title Blood Pressure Response Rate at Weeks 28 and 52
Hide Description 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).
Time Frame Weeks 28 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 508
Measure Type: Number
Unit of Measure: percentage of subjects
Week 28 86.6
Week 52 86.2
Time Frame Treatment Emergent Adverse Events (TEAEs) were collected from the time of first study drug administration up to 7 days after Week 52/EOS
Adverse Event Reporting Description One death reported under SAE happened approximately 6 months after the subject had completed the study due to malignant melanoma of head and neck with metastasis to lung and liver, not related to the treatment.
 
Arm/Group Title Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Hide Arm/Group Description 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).
All-Cause Mortality
Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Affected / at Risk (%) # Events
Total   15/508 (2.95%)    
Blood and lymphatic system disorders   
Aplastic anaemia  1  1/508 (0.20%)  1
Cardiac disorders   
Acute myocardial infarction  1  1/508 (0.20%)  1
Coronary artery disease  1  1/508 (0.20%)  1
Supraventricular tachycardia  1  1/508 (0.20%)  1
Gastrointestinal disorders   
Colitis  1  1/508 (0.20%)  1
General disorders   
Chest pain  1  1/508 (0.20%)  1
Pyrexia  1  1/508 (0.20%)  1
Infections and infestations   
Chronic sinusitis  1  1/508 (0.20%)  1
Injury, poisoning and procedural complications   
Ankle fracture  1  1/508 (0.20%)  1
Joint dislocation  1  1/508 (0.20%)  2
Musculoskeletal and connective tissue disorders   
Back pain  1  1/508 (0.20%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Acute myeloid leukaemia  1  1/508 (0.20%)  1
Malignant melanoma  1  1/508 (0.20%)  1
Prostate cancer  1  1/508 (0.20%)  1
Nervous system disorders   
Syncope  1  1/508 (0.20%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Nifedipine GITS/Candesartan Cilexetil FDC (BAY98-7106)
Affected / at Risk (%) # Events
Total   279/508 (54.92%)    
General disorders   
Fatigue  1  18/508 (3.54%)  20
Oedema  1  55/508 (10.83%)  80
Oedema peripheral  1  150/508 (29.53%)  239
Infections and infestations   
Nasopharyngitis  1  27/508 (5.31%)  30
Upper respiratory tract infection  1  25/508 (4.92%)  29
Nervous system disorders   
Dizziness  1  47/508 (9.25%)  55
Headache  1  47/508 (9.25%)  60
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: Bayer HealthCare AG
EMail: clinical-trials-contact@bayerhealthcare.com
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01788358     History of Changes
Other Study ID Numbers: 14801
2012-004515-32 ( EudraCT Number )
First Submitted: February 7, 2013
First Posted: February 11, 2013
Results First Submitted: July 21, 2015
Results First Posted: August 17, 2015
Last Update Posted: October 24, 2017