Long Term Study of Solifenacin Succinate and Tamsulosin Hydrochloride Oral Controlled Absorption System (OCAS) in Males With Lower Urinary Tract Symptoms (Neptune II)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier:
NCT01021332
First received: November 24, 2009
Last updated: December 16, 2015
Last verified: December 2015
  Purpose
Clinical study to examine the safety, tolerability and efficacy of long-term combination therapy of tamsulosin and solifenacin in the treatment of males with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) with a substantial storage component.

Condition Intervention Phase
Lower Urinary Tract Symptoms
Benign Prostatic Hyperplasia
Drug: tamsulosin hydrochloride/solifenacin succinate fixed dose combination (0.4 mg/6 mg)
Drug: tamsulosin hydrochloride/solifenacin succinate fixed dose combination (0.4 mg/9 mg)
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Long Term, Multi-center Study to Assess the Safety and Efficacy of Fixed Dose Combinations of Solifenacin Succinate (6 mg and 9 mg) With Tamsulosin Hydrochloride OCAS 0.4 mg, in Male Subjects With Lower Urinary Tract Symptoms (LUTS) Associated With Benign Prostatic Hyperplasia (BPH) With a Substantial Storage Component

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AEs) [ Time Frame: From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks) ] [ Designated as safety issue: Yes ]
    Safety is monitored by collecting AEs, which include abnormal lab parameters, vital signs or ECG data if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study drug or was clinically significant. A serious AE (SAE) was an AE resulting in death, persistent or significant disability/incapacity or congenital anomaly/birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs were assessed by the Investigator for intensity (mild-no disruption of normal daily activities, moderate-affected normal daily activities or severe-inability to perform daily activities) and for causal relationship to study drug. A treatment-emergent adverse event (TEAE) was defined as an AE that occurred after the intake of first dose of double-blind study drug (if on FDC in 905-CL-055) or after first open-label dose until 30 days after the last dose of open-label study drug (in 905-CL-057).

  • Change From Baseline to End of Treatment in Post Void Residual (PVR) Volume [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    PVR volume is the volume of urine retained after voiding. PVR volume was assessed by ultrasonography or bladder scan.

  • Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    Qmax during a micturition (urination) was recorded using uroflowmetry.

  • Change From Baseline to End of Treatment in Average Flow Rate (Qmean) [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    Qmean during a micturition (urination) was recorded using uroflowmetry.

  • Change From Baseline to End of Treatment in Total International Prostate Symptom Score (IPSS) [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]

    The International Prostate Symptom Score (IPSS) is a validated global questionnaire to assess the degree of urinary symptoms, based on answers to 7 questions concerning urinary symptoms:

    • Incomplete emptying of the bladder
    • Intermittency
    • Weak stream
    • Hesitancy
    • Frequency
    • Urgency
    • Nocturia Each question is assigned points from 0 to 5 indicating increasing severity of the symptom. Total score can range from 0 to 35 (mildly symptomatic to severely symptomatic).

  • Change From Baseline to End of Treatment in Total Urgency Frequency Score (TUFS) (Previously Known as Total Urgency Score [TUS]) [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]

    The Patient Perception of the Intensity of Urgency Scale (PPIUS) is a validated scale completed as part of the micturition diary. For each micturition and/or incontinence episode, the participant rated the degree of associated urgency according to the following 5-point categorical scale:

    • 0. No urgency;
    • 1. Mild urgency;
    • 2. Moderate urgency;
    • 3. Severe urgency;
    • 4. Urgency incontinence TUS/TUFS was calculated as the sum of the PPIUS gradings from the 3-day diary divided by the number of days on which urgency grading was recorded. Higher scores indicate more severe urgency.


Secondary Outcome Measures:
  • Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    A micturition is any voluntary urination, excluding episodes of incontinence only.The mean number of micturitions per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

  • Change From Baseline to End of Treatment in Mean Voided Volume Per Micturition [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    A micturition is any voluntary urination, excluding episodes of incontinence only. The mean volume voided per micturition was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

  • Change From Baseline to End of Treatment in Maximum Volume Voided Per Micturition [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    A micturition is any voluntary urination, excluding episodes of incontinence only. The maximum volume voided per micturition was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

  • Change From Baseline to End of Treatment in Mean Number of Urgency Episodes (PPIUS Grade 3 or 4) Per 24 Hours [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    An urgency episode is defined as an episode of strong desire to void accompanied by fear of leakage or pain. The mean number of urgency episodes with PPIUS grade 3 (Severe urgency) or 4 (Urgency incontinence) per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

  • Change From Baseline to End of Treatment in Mean Number of Urgency Incontinence Episodes Per 24 Hours [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    An urgency incontinence episode is defined as an episode with any involuntary leakage of urine accompanied by or immediately preceded by urgency. The mean number of urgency incontinence episodes with PPIUS grade 3 (Severe incontinence) or 4 (Urgency incontinence) per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

  • Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    An incontinence episode is defined as an episode with any involuntary loss of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

  • Change From Baseline to End of Treatment in Mean Number of Nocturia Episodes Per 24 Hours [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    A nocturia episode is defined as waking up at night to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the patient gets up in the morning with the intention to stay awake). The mean number of nocturia episodes per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

  • Change From Baseline to End of Treatment in Mean Number of Pads Used Per 24 Hours [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    The mean number of pads per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

  • Change From Baseline to End of Treatment in IPSS Voiding Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    The IPSS is a validated global questionnaire to assess the degree of urinary symptoms based on answers to 7 questions. Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The voiding score is the sum of the responses to 4 voiding questions (incomplete emptying of the bladder, intermittency, weak stream, hesitancy) and ranges from 0 to 20 (mildly symptomatic to severely symptomatic).

  • Change From Baseline to End of Treatment in IPSS Storage Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    The IPSS is a validated global questionnaire to assess the degree of urinary symptoms based on answers to 7 questions concerning urinary symptoms. Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The storage symptom score is the sum of the responses to 3 storage questions (frequency,urgency and nocturia) and ranges from 0 to 15 (mildly symptomatic to severely symptomatic).

  • Change From Baseline to End of Treatment in IPSS Quality of Life (QoL) Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    The QoL assessment was a single question asking the participant how he would feel about tolerating his current level of symptoms for the rest of his life. The answers ranged from 0 to 6 (delighted to terrible).

  • Change From Baseline to End of Treatment in Individual IPSS Scores [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]

    The IPSS is a validated global questionnaire to assess the degree of urinary symptoms, based on answers to 7 questions concerning urinary symptoms:

    • Incomplete emptying of the bladder
    • Intermittency
    • Weak stream
    • Hesitancy
    • Frequency
    • Urgency
    • Nocturia

    Each question is assigned points from 0 to 5 indicating increasing severity of the symptom.


  • Change From Baseline to End of Treatment in Symptom Bother Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The Symptom Bother portion consists of an 8-item scale scored from 1 to 6.The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 to 100, with 100 indicating worst severity. A negative change from baseline indicates an improvement.

  • Change From Baseline to End of Treatment in Health-related Quality of Life (HRQoL) Subscale: Coping Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]

    The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6:

    • coping
    • concern
    • sleep
    • social interaction

    Coping score can range from 8 to 48 (none of the time to all of the time) and transformed to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement.


  • Change From Baseline to End of Treatment in Health-related Quality of Life (HRQoL) Subscale: Concern Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]

    The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6:

    • coping
    • concern
    • sleep
    • social interaction

    Concern score can range from 8 to 48 (none of the time to all of the time) and transformed to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement.


  • Change From Baseline to End of Treatment in Health-related Quality of Life (HRQoL) Subscale: Sleep Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]

    The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6:

    • coping
    • concern
    • sleep
    • social interaction

    Sleep score can range from 8 to 48 (none of the time to all of the time) and transformed to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement.


  • Change From Baseline to End of Treatment in Health-related Quality of Life (HRQoL) Subscale: Social Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]

    The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6:

    • coping
    • concern
    • sleep
    • social interaction

    Social score can range from 8 to 48 (none of the time to all of the time) and transformed to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement.


  • Change From Baseline to End of Treatment in Health-related Quality of Life (HRQoL) Subscale: Total Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]

    The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6:

    • coping
    • concern
    • sleep
    • social interaction

    Total score is calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement.


  • Number of OAB-q Responders Based on Health-related Quality of Life: Total Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    A OAB-q responder was defined as a participant with an improvement from baseline in HRQoL subscale total score ≥ 10.

  • Change From Baseline to End of Treatment in EQ-5D Mobility Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]

    The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains:

    • mobility
    • self-care
    • usual activity
    • pain/discomfort
    • anxiety/depression

    Each domain has 3 response levels (1= no problem, 2= some problems, 3 = confined to bed).


  • Change From Baseline to End of Treatment in EQ-5D Self-care Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]

    The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains:

    • mobility
    • self-care
    • usual activity
    • pain/discomfort
    • anxiety/depression

    Each domain has 3 response levels (1= no problem, 2= some problems, 3 = unable to wash/dress).


  • Change From Baseline to End of Treatment in EQ-5D Usual Activities Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]

    The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains:

    • mobility
    • self-care
    • usual activity
    • pain/discomfort
    • anxiety/depression

    Each domain has 3 response levels (1= no problem, 2= some problems, 3 = unable to perform usual activities).


  • Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]

    The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains:

    • mobility
    • self-care
    • usual activity
    • pain/discomfort
    • anxiety/depression

    Each domain has 3 response levels (1= no pain, 2= moderate pain, 3 = extreme pain).


  • Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]

    The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains:

    • mobility
    • self-care
    • usual activity
    • pain/discomfort
    • anxiety/depression

    Each domain has 3 response levels (1= not anxious, 2= moderately anxious, 3 = extremely anxious).


  • Change From Baseline to End of Treatment in EQ-5D Visual Analogue Scale (VAS) Score [ Time Frame: Baseline and up to 52 weeks of FDC treatment ] [ Designated as safety issue: No ]
    Visual Analogue Scale (VAS) is part of the EQ-5D questionnaire. The VAS is self-rated by the participant ranging from 0 to 100 (worst imaginable health state to best imaginable health state).


Enrollment: 1067
Study Start Date: April 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Total Group
Participants who received at least one dose of open-label fixed dose combination (FDC) treatment
Drug: tamsulosin hydrochloride/solifenacin succinate fixed dose combination (0.4 mg/6 mg)
oral
Other Names:
  • EC905
  • Vesomni
Drug: tamsulosin hydrochloride/solifenacin succinate fixed dose combination (0.4 mg/9 mg)
oral
Other Name: EC905

Detailed Description:
This is an open-label extension study following the double blind 905-CL-055 study
  Eligibility

Ages Eligible for Study:   45 Years and older   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Completion of 12 weeks double-blind treatment in Study 905-CL-055

Exclusion Criteria:

  • Any significant PVR volume (>150 mL)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01021332

  Show 70 Study Locations
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Investigators
Study Chair: Use Central Contact Astellas Pharma Global Development
  More Information

Additional Information:
Responsible Party: Astellas Pharma Europe B.V.
ClinicalTrials.gov Identifier: NCT01021332     History of Changes
Other Study ID Numbers: 905-CL-057  2008-001212-20 
Study First Received: November 24, 2009
Results First Received: October 14, 2015
Last Updated: December 16, 2015
Health Authority: Austria: Federal Office for Safety in Health Care
Belarus: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: Ethics Committee
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Astellas Pharma Inc:
Lower Urinary Tract Symptoms
Treatment
Solifenacin succinate
Tamsulosin hydrochloride OCAS
Benign Prostatic Hyperplasia
EC905
Vesomni

Additional relevant MeSH terms:
Hyperplasia
Prostatic Hyperplasia
Lower Urinary Tract Symptoms
Pathologic Processes
Prostatic Diseases
Genital Diseases, Male
Urological Manifestations
Signs and Symptoms
Solifenacin Succinate
Tamsulosin
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Urological Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents

ClinicalTrials.gov processed this record on July 28, 2016