Safety and Efficacy of 0.5mg Dutasteride and 0.4mg Tamsulosin Combination Once Daily for Six Months for Benign Prostatic Hyperplasia

NCT01673490 | Terminated Phase 4 Results

• 1 other identifier: 114785
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

Open-label, 6 month-treatment with the IP in all subjects. - Sample size: A total of 90 subjects will be enrolled so that among them at least 57 will complete the 6-month treatment period and evaluable for analysis.

• Primary objective: To assess the safety of 0.5 mg dutasteride/0.4 mg tamsulosin combination therapy for six month in BPH patients by monitoring category, frequency and severity of adverse events encountered during the treatment period.
• Secondary objective: To assess the efficacy of 0.5 mg dutasteride/0.4 mg tamsulosin combination therapy with regard to symptom improvement in BPH patients by monitoring and analyzing of changes in IPSS and Qmax after 6 months of treatment.

Conditions

Prostatic Hyperplasia

Keywords

Benign Prostatic Hyperplasia; dutasteride and tamsulosin

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Any On-treatment Adverse Events (AEs) or Any Serious Adverse Event (SAEs) and Treatment-related AEs

  An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product at any dose, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that jeopardizes the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, and is associated with liver injury and impaired liver function.

  From start of study medication until follow-up (up to 7 months)

• Number of Participants With Any Post-treatment Adverse Events (AEs) or Any Serious Adverse Event (SAEs) and Treatment-related AEs

  An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product at any dose, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that jeopardizes the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, and is associated with liver injury and impaired liver function.

  From start of study medication until follow-up (up to 7 months)

• Number of Participants With Abnormal Electrocardiogram (ECG) Findings at the Indicated Time Points

  A 12 lead ECG was measured at Screening, Month 1 (Visit 1), Month 3 (Visit 3) and Month 6 (Visit 5).

  Screening, Month 1, Month 3 and Month 6

• Number of Participants With Clinical Chemistry Values Shift From Normal at Baseline to Abnormal at Any Time Post-Baseline

  Blood samples were collected at Screening, Month 1 (Visit 1), Month 3 (Visit 3) and Month 6 (Visit 5) for chemistry laboratory assessments. Clinical chemistry parameters included alanine aminotrasferase (ALT), aspartate aminotrasferase (AST), creatinine, glucose, potassium, protein, sodium and urea. The number of participants with a shift from normal at Baseline to abnormal at any time post-Baseline for a clinical chemistry parameter are summarized.

  Screening, Month 1, Month 3 and Month 6

• Number of Participants With Hematology Values Shift From Normal at Baseline to Abnormal at Any Time Post-Baseline

  Blood samples were collected at Screening, Month 3 (Visit 3) and Month 6 (Visit 5) for hematology laboratory assessments. Hematology parameters included basophils, leukocytes, hemoglobin (HGB), eosinophils, erythrocytes (ery), ery mean Corpuscular HGB concentration, ery mean corpuscular HGB, ery distribution width, lymphocytes, hematocrit, monocytes, neutrophils and platelets. The number of participants with a shift from normal at Baseline to abnormal at any time post-Baseline for hematology parameters are summarized.

  Screening, Month 3 and Month 6

• Number Participants With a Negative or Positive Response at the Indicated Time Points

  Urine samples were collected at Screening (SC), Month 3 (3M) and Month 6 (6M) for urinalysis laboratory assesment. Final value (FV) is defined as the latest post-Baseline value available in the study for each parameter.Urinalysis parameters included erythrocytes, glucose, ketones, leukocytes and protein. Number of participants with a negative (NEG) or positive (POS) response at the indicated time points are summarized.

  Screening, Month 3 and Month 6

• Change From Baseline in Total Prostate -Specific Antigen (PSA) at the Indicated Time Points

  Serum sample was collected at Baseline, Month 3 and Month 6 for assesment of total PSA. PSA is a substance produced by prostate gland, and the elevated level of PSA indicates prostate cancer or any other non-cancerous condition related to prostate. Change from Baseline in total PSA at Month 3 and Month 6 was calculated as value at specified visist minus Baseline value.

  Baseline, Month 3 and Month 6

• Free to Total PSA Ratio at the Indicated Time Points

  Serum sample was collected at Screening (Baseline for participants with Free to Total PSA ratio at Month 6), and Month 6 for assessment of free to total PSA ratio. PSA is a substance produced by prostate gland, and the elevated level of PSA indicates prostate cancer or any other non-cancerous condition related to prostate. Free to total PSA ratio at Baseline for participants with free to total PSA Ratio at Month 6 and free to total PSA ratio at month 6 are presented.

  Baseline, Month 6

Secondary Outcomes (2)

• Change From Baseline in the International Prostate Symptom Score (IPSS) at Month 6

  Baseline and Month 6

• Change From Baseline in Maximum Rate of Urinary Flow (Qmax) at the Indicated Time Points

  Baseline, Month 3 and Month 6

Study Arms (1)

Combodart/Duodart

EXPERIMENTAL

Single arm testing the efficacy/safety of the combinnation of Dutasteride/Tamsulosin

Drug: Dutasteride/Tamsulosin

Interventions

Dutasteride/Tamsulosin DRUG

0.5 mg dutasteride/ 0.4 mg tamsulosin once daily for the duration of 180 day -treatment

Also known as: Duodart, combodart

Combodart/Duodart

Eligibility Criteria

• Age: 50 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male, age ≥ 50 years. Clinical diagnosis of benign prostate hypertrophy (BPH) . International Prostate Symptom Score (IPSS) ≥ 12 Prostate volume ≥30 ml (transrectal ultrasonography). Total serum prostate specific antigen (PSA) ≥1.5 ng/mL and ≤10 ng/mL. Free-to-total PSA ratio \> 20% Maximum flow rate (Qmax) \>5 mL/sec and ≤15 mL/sec and post-void residual volume of \< 150 mL Willing and able to give written informed consent and comply with study procedures throughout study Able to swallow and retain oral medication Able to express personal thought and feeling Ability to read and comprehend information on the Sexual Function Inventory

You may not qualify if:

• History or evidence of prostate cancer (e.g. positive biopsy or ultrasound, suspicious digital rectal examination).
• Previous prostatic surgery (TURP, balloon dilatation, thermotherapy and stent replacement) or other invasive procedures to treat BPH.
• History of flexible/rigid cystoscopy or other instrumentation of the urethra within past 7 days History of acute urine retention (AUR) within past 3 months. Any causes other than BPH result in urinary symptoms or changes in flow rate (e.g. neurogenic bladder, bladder neck contracture, urethral stricture, bladder malignancy, acute or chronic prostatitis, acute or chronic urinary tract infections).
• History of breast cancer or clinical finding suggestive of malignancy. Use of any 5-alpha-reductase inhibitor (e.g. Proscar®, Propecia®), drugs with antiandrogenic properties (e.g. spironolactone, flutamide, bicalutamide, cimetidine, ketoconazole, progestational agents), drugs which induce gynecomastia or drugs which affect prostate volume, within past 6 months and throughout the study (other than as study medication). Do not use dutasteride within past 12 months. Do not use metronidazole for a long time.
• Concurrent use of anabolic steroids (eg. Durabolin®). Use of phytotherapy (eg: Tadenan®, Permixon®, etc) for BPH within 2 weeks of screening visit and/or predicted to need phytotherapy during the study.
• Use of any alpha-adrenoreceptor blockers (i.e. indoramin, prazosin, terazosin, tamsulosin, alfuzosin and doxazosin) within 2 weeks of screening visit and/or predicted to need any alpha blockers other than tamsulosin during the study.
• Use of any alpha-adrenoreceptor agonists (e.g. pseudoephedrine, phenylephrine, ephedrine) or anticholinergics (e.g. oxybutynin, propantheline) or cholinergics (e.g. bethanecol chloride) within 48 hours prior to all uroflowmetry assessments.
• Hypersensitivity to any alpha-/beta-adrenoreceptor blocker or 5-alpha-reductase inhibitor, or other chemically-related drugs.
• Concurrent use of drugs known or thought to have an interaction with tamsulosin and dutasteride.
• History of hepatic impairment or abnormal liver function tests at screening (defined ALT, AST, and/or alkaline phosphatase \>2 times the upper limit of normal, or total bilirubin \>1.5 times the upper limit of normal).
• History of renal insufficiency, or serum creatinine \>1.5 times the upper limit of normal at screening.
• History of malignancies other than basal cell carcinoma or squamous cell carcinoma of the skin within the past 5 years. Subjects with a prior malignancy who have had no evidence of disease for at least 5 years prior to screening are eligible.
• Any unstable, serious co-existing medical condition(s) including, but not limited to, myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within past 6 months; medically uncontrollable diabetes or peptic ulcer disease History of postural hypotension, dizziness, vertigo or any signs and symptoms of orthostasis, which in judgments of investigator, could be exacerbated by tamsulosin History of unsuccessful treatment with tamsulosin or 'first dose' hypotensive episode on initiation of alpha-1-adrenoreceptor antagonist therapy.
• History of unsuccessful treatment with finasteride or dutasteride. Willing to have a child during the treatment period or within 6 months thereafter Having female partner who is a pregnant woman or in child-bearing age and refuse to use condom for sexual protection Willing to donate blood during treatment period or within 6 months thereafter. History or current evidence of drug or alcohol abuse within past 12 months. History of any illness might confound the results of the study or poses additional risk to the patient.
• Participation in investigational or marketed drug trial within 30 days preceding the screening visit and/or during the study treatment

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Ho Chi Minh City, Vietnam

Location

Related Links

• IPD for this study will be made available via the Clinical Study Data Request site.

MeSH Terms

Conditions

Prostatic Hyperplasia

Interventions

Dutasteride; Tamsulosin

Condition Hierarchy (Ancestors)

Prostatic Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Azasteroids; Steroids, Heterocyclic; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2012
• First Posted: August 28, 2012
• Study Start: June 29, 2012
• Primary Completion: March 20, 2015
• Study Completion: March 20, 2015
• Last Updated: August 20, 2018
• Results First Posted: December 17, 2015

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

VN (1)