A Clinical Study to Investigate the Efficacy, Safety and Pharmacokinetics of ASP3652 in Patients With Chronic Abacterial Prostatitis / Chronic Pelvic Pain Syndrome (CP/CPPS) (AZURE)

A Phase II, Randomized, Double-blind, Placebo-controlled, Parallel Group, Adaptive, Combined Proof of Concept and Dose-Finding Study to Investigate Efficacy, Safety, Pharmacodynamics and Pharmacokinetics of ASP3652 in the Treatment of CP/CPPS

In this study several doses of ASP3652, given orally for 12 weeks, will be compared with placebo in the treatment of patients with Chronic abacterial Prostatitis / Chronic Pelvic Pain Syndrome.

Study Overview

• Status: Completed
• Conditions: Chronic Pelvic Pain Syndrome; Chronic Abacterial Prostatitis
• Intervention / Treatment: Drug: Placebo; Drug: ASP3652

Detailed Description

This study will investigate the efficacy of ASP3652 in the treatment of patients with Chronic abacterial Prostatitis / Chronic Pelvic Pain Syndrome (CP/CPPS). In comparison with placebo, ASP3652 will be given in different dosages orally for 12 weeks. The aims are to investigate efficacy of ASP3652 in CP/CPPS, to assess the optimal dose of ASP3652, to investigate safety and tolerability and to investigate pharmacokinetics and pharmacodynamics of ASP3652 in patients with CP/CPPS in and out-patients setting.

• Study Type: Interventional
• Enrollment (Actual): 239
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czech Republic
  • Hradec Kralove, Czech Republic, 50005
    • Site: 3105 - Fakultni nemocnice Hradec Kralove
  • Kolin, Czech Republic, 28000
    • Site: 3106 - Urologicke oddeleniUsti nad Labem
  • Kromeriz, Czech Republic, 76755
    • Site: 3109- Hospital Kromeriz
  • Novy Jicin, Czech Republic, 74101
    • Site: 3107 - Urologie
  • Olomouc, Czech Republic, 77200
    • Site: 3103 - Fakultni nemocnice Olomouc
  • Plzen, Czech Republic, 30100
    • Site: 3111 - Urology center
  • Praha, Czech Republic, 14000
    • Site: 3112 - Urosante
  • Praha 6, Czech Republic, 16000
    • Site: 3102 - Androgeos
  • Sternberk, Czech Republic, 78501
    • Site: 3110 - Urologicka ordinace
  • Uherske Hradiste, Czech Republic, 68668
    • Site: 3104 - Uherskohradistska nemocnice a.s.
  • Usti nad Labem, Czech Republic, 40113
    • Site: 3101- Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z.
  • Zatec, Czech Republic, 43801
    • Site: 3113 - Urologicka ambulance
• Germany
  • Berlin, Germany, 10719
    • Site: 3212 - Urologische Praxis
  • Berlin, Germany, 12200
    • Site: 3214 - Charité Campus Benjamin Franklin
  • Borken, Germany, 46325
    • Site: 3208 - Private Praxis Urologie Borken
  • Buchholz, Germany, 21244
    • Site: 3202 - Urologische Praxis
  • Giessen, Germany, 35392
    • Site: 3201 - Universitats klinikum Giessen und Marburg
  • Hamburg, Germany, 22587
    • Site: 3203 - Urologische Praxis
  • Herzogenaurach, Germany, 91074
    • Site: 3211 - Urologische Gemeinschaftspraxis
  • Holzminden, Germany, 37603
    • Site: 3205 - Gesundheitszentrum Holzminden
  • Kempen, Germany, 47906
    • Site: 3213 - Urologische Praxis
  • Leipzig, Germany, 04179
    • Site: 3206 - Private Praxis
  • Marburg, Germany, 35039
    • Site: 3210 - Private Praxis
  • Markkleeberg, Germany, 04416
    • Site: 3207 - Private Praxis
  • Neunkirchen, Germany, 66538
    • Site: 3204 - Akademisches Lehrkrankenhaus
  • Reutlingen, Germany, 72764
    • Site: 3215 - Urologische Praxis
  • Sangerhausen, Germany, 06526
    • Site: 3209 - Private Praxis
• Latvia
  • Jelgava, Latvia, LV-3001
    • Site: 3302 - Jelgava Outpatient Clinic
  • Liepaja, Latvia, LV-3401
    • Site: 3301 - Litavniece Urologist Private Practice
  • Riga, Latvia, LV-1002
    • Site: 3303 - P. Stradins Clinical University Hospital
  • Ventspils, Latvia, LV-3601
    • Site: 3304 - Nord Kurzeme Regional Hospital
• Lithuania
  • Kaunas, Lithuania, LT-50154
    • Site: 3404 - Motina ir vaikas clinic
  • Vilnius, Lithuania, LT-08661
    • Site: 3402 - Vilnius Univeristy Hospital "Santariskiu Klinikos" Urology Centre
  • Vilnius, Lithuania, LT-09108
    • Site: 3401 - Clinics "Privatus gydytojas"
  • Vilnius, Lithuania, LT-10207
    • Site: 3403 - Public Institution Vilnius City University Hospital
• Poland
  • Chorzow, Poland, 41-500
    • Site: 3503 - Urovita Sp.z.o.o. NZOZ Szpital Slaskie Centrum Urologii
  • Lodz, Poland, 90-302
    • Site: 3504 - Centrum Medyczne Szpital Sw Rodziny Sp z o.o.
  • Lotum, Poland, 87-100
    • Site: 3509 - NZOZ Nasz Lekarz, Praktyka Grupowa Lekarzy Rodzinnych z Przychodnia Specjalistyczna
  • Piaseczno, Poland, 05-500
    • Site: 3510 - Heureka Hanna Szalecka
  • Poznan, Poland, 61-397
    • Site: 3501 - Indywidualna Specjalistyczna Praktyka Lekarska
  • Siedlce, Poland, 08-110
    • Site: 3511 - Urologica Praktyka Lekarska Adam Marcheluk
  • Warszawa, Poland, 01-432
    • Site: 3508 - NZOZ Centrum Medyczna Wola
  • Warszawa, Poland, 02-005
    • Site: 3507 - Szpital Kliniczny Dzieciatka Jezus Centrum Leczenia Obrazen
  • Wroclaw, Poland, 51-124
    • Site: 3502 - Wojewodzki Szpital Specjalistyczny we Wroclawiu
  • Wroclaw, Poland, 54-144
    • Site: 3505 - EMC Instytut Medyczny SA
  • Wroclaw, Poland, 54-239
    • Site: 3506 - Specjalistyczna Praktyka Lekarska Gabinet Urologiczny
• Spain
  • Barcelona, Spain, 8970
    • Site: 3701 - Hospital Moises Broggi de Sant Joa
  • Barcelona, Spain, CP: 08025
    • Site: 3703 - Fundació Puigvert
  • Coslada, Spain, CP:28822
    • Site: 3702 - Hospital del Henares

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Is diagnosed with CP/CPPS with symptoms for at least 3 months over the last 6 months
• Has a NIH-CPSI total score of at least 15
• A score of at least 4 on question 4 (pain) in the NIH-CPSI
• Reports pain on palpation of the prostate or the perineum/genital area
• Answers "yes" to at least 1 out of 6 items in question 1 and 2 of the NIH-CPSI
• Is willing to comply with study requirements such as completing the micturition and symptoms diary and attend all study visits

Exclusion Criteria:

• Isolated unilateral testicular, penile or scrotal pain as a solitary symptom of pelvic pain
• Urinary Tract Infection (UTI) or prostate infection found at screening using the pre- and post massage test or in the last 3 months prior to screening
• Any prior prostate and or bladder intervention within 3 months prior to screening
• Lower urinary tract malignancy (suspected), such as positive (micro) hematuria in urine sediment or Prostate Specific Antigen (PSA) >4 ng/mL
• Symptomatic urethral stricture or symptomatic bladder or urethral calculi, severe bladder outlet obstruction, overactive bladder with incontinence or Post Void Residual volume, greater than 150 mL
• Clinically significant abnormalities on transabdominal ultrasound of bladder and prostate or neurological disease or defect affecting bladder function
• Currently active sexually transmittable disease
• Substance abuse or any use of delta-9-tetrahydrocannabinol (THC) as assessed by a positive urine test for THC at screening
• Major depression, i.e. a Center for Epidemiological Studies Depression Scale score of 27 or more
• Any clinically relevant concomitant disease (past or present) which would, in the opinion of the investigator, put the subject at risk or mask measures of efficacy
• Use of steroids, immunomodulators, anticonvulsants, cytochrome P4502C8 inhibitors, cannabis/THC based medication, opioid analgetics or antiviral/antimicrobial/antifungal agents during the last 4 weeks before screening
• Initiation, discontinuation, or variation in the dose of antidepressants, alpha-blockers, 5-alpha reductase inhibitors, antimuscarinics, benzodiazepines, skeletal muscle relaxants, non-steroidal antiinflammatory drugs, non-opioid analgetics and herbal therapies during the last 4 weeks before screening. Subjects should continue these medications at that same stable dose throughout the study
• Clinically relevant abnormal urine or blood safety laboratory values or active hepatic and/or biliary disease (AST or ALT should not be >3 times the upper limit of normal, total bilirubin should not be >2 times the upper limit of normal)
• Participated in any clinical study or has been treated with any investigational drug or device within 30 days prior to screening, or the period stipulated by local regulations, whichever is longer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Oral
Experimental: Lowest dose ASP3652 twice daily	Drug: ASP3652; Oral
Experimental: Low dose ASP3652 twice daily	Drug: ASP3652; Oral
Experimental: Medium dose ASP3652 twice daily	Drug: ASP3652; Oral
Experimental: High dose ASP3652 once daily	Drug: ASP3652; Oral
Experimental: High dose ASP3652 twice daily	Drug: ASP3652; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), total score at 12 weeks	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the NIH-CPSI pain domain score at week 12		Baseline and 12 weeks
Change from baseline in NIH-CPSI total score at 4 and 8 weeks and at 2 weeks follow-up after treatment		Baseline, 4 weeks, 8 weeks and 2 weeks follow-up post treatment
Change from baseline in NIH-CPSI pain domain at week 4 and 8 and at 2 weeks follow-up after treatment		Baseline, 4 weeks, 8 weeks 2 weeks follow-up post treatment
Change from baseline in NIH-CPSI urinary symptoms domain at week 4, 8 and 12 and at 2 weeks follow-up after treatment		Baseline, 4 weeks, 8 weeks and 12 weeks treatment and weeks 2 weeks follow-up post treatment
Change from baseline in NIH-CPSI Quality of Life impact domain at week 4, 8 and 12 and at 2 weeks follow-up after treatment		Baseline, 4 weeks, 8 weeks and 12 weeks treatment and weeks 2 weeks follow-up post treatment
Global Response Assessment at week 4, 8 and 12 and at 2 weeks follow-up post treatment		Baseline, 4 weeks, 8 weeks and 12 weeks treatment and at 2 weeks follow-up post treatment
The proportion of Clinical Responders	Composite of two definitions are used: subjects who showed at least 4 points decrease in NIH-CPSI total score at 12 weeks compared to baseline and subjects who showed at least 6 points decrease in NIH-CPSI total score at 12 weeks	12 weeks
Genitourinary pain index (GUPI) total score, sub domain and responders, at week 12	Responder defined as 7 points or more decrease from baseline	12 weeks
Mean daily CPSI-24hour total score at baseline and at 4, 8 and 12 weeks and 2 weeks follow-up post treatment		Baseline, 4 weeks, 8 weeks and 12 weeks and 2 weeks follow-up post treatment
Mean daily pain for the 7 days period prior to attending study visits at baseline and at 4, 8 and 12 weeks and 2 weeks follow-up post treatment		Baseline, 4 weeks, 8 weeks and 12 weeks and 2 weeks follow-up post treatment
Short form McGill pain questionnaire: sensory, affective and total score, VAS, present pain intensity at baseline and at 12 weeks		Baseline and 12 weeks
Voiding: mean number of micturitions per 24 hours and per night, mean number of urgency episodes per 24 hours and mean level of urgency per micturition	Based on daily urinary symptom diary for 3 consecutive days in the weeks prior to the visits at baseline, 4 and 12 weeks treatment	Baseline, 4 weeks and 12 weeks treatment
International Prostate Symptom Score at screening and at 12 weeks		Screening and 12 weeks
European Quality of Life questionnaire in 5 dimensions (EQ-5D) at baseline and at 12 weeks		Baseline and 12 weeks
Male sexual health questionnaire at baseline and at 12 weeks		Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Executive Director Global Medical Science, Astellas Pharma Europe B.V.; Principal Investigator: Coordination Investigator, Clinic for Urology, Pediatric Urology and Andrology, Germany

Publications and helpful links

General Publications

• Martina R, Houbiers J, Melis J, van Till O. A combined proof of concept and dose finding study with multiple endpoints: A Bayesian adaptive design in chronic prostatitis/chronic pelvic pain syndrome. Biom J. 2019 May;61(3):476-487. doi: 10.1002/bimj.201700210. Epub 2018 Sep 3.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: July 8, 2011
• First Submitted That Met QC Criteria: July 8, 2011
• First Posted (Estimate): July 12, 2011

Study Record Updates

• Last Update Posted (Estimate): March 21, 2013
• Last Update Submitted That Met QC Criteria: March 19, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Chronic; Pelvic Pain; Prostatitis; NIH-CPSI; Pain domain score in NIH-CPSI
• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Disease; Prostatic Diseases; Syndrome; Pelvic Pain; Prostatitis
• Other Study ID Numbers: 3652-CL-0019; 2010-023775-25 (EudraCT Number)