A Study to Evaluate Tolerability and Participants Preference Between Mirabegron and Tolterodine Extended Release (ER) in Participants With Overactive Bladder (OAB) (PREFER)

Astellas

Status and phase: Completed; Phase 4

Conditions: Overactive Bladder (OAB)

Treatments: Drug: Mirabegron; Drug: Tolterodine ER

Study type: Interventional

Funder types: Industry

Identifiers

NCT02138747

178-MA-1001

Details and patient eligibility

About

The purpose of this study was to assess tolerability of mirabegron compared to tolterodine ER in the treatment of participants with symptoms of Overactive Bladder (OAB) as well as the impact of treatment on micturition frequency and incontinence episodes.

Full description

The study consisted of two double-blind treatment periods with a wash-out period in between.

Enrollment: 376 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant is willing and able to complete the micturition diary and questionnaires correctly.

• Participant has symptoms of OAB (urinary frequency and urgency with or without incontinence) for greater than or equal to 3 months prior to Screening.

• Participant must be treatment-naïve to pharmaceutical agents for OAB.

• Female participant must not donate ova starting at Screening and throughout the study period, and for 30 days after the final study drug administration.

• Male participant must not donate sperm starting at Screening and throughout the study period and for at least 30 days after final study drug administration.

• Participant agrees not to participate in another interventional study from the time of screening until the final study visit.

• Inclusion Criteria assessed at Visit 2 (Week 0) based on the 3-day micturition diary:

  • Participant continues to meet all inclusion criteria of Visit 1.
  • Participant must experience at least 3 episodes of urgency (grade 3 or 4) during the 3 day micturition diary.
  • Participant must experience an average of greater than or equal to 8 micturitions/day on the 3 day micturition diary

Exclusion criteria

• Female participant who is lactating or is intending to breastfeed during the study period and for 30 days after the final study visit.

• The participant has clinically significant bladder outlet obstruction (BOO) posing a risk of urinary retention.

• Participant has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor.

• Participant has evidence of Urinary Tract Infection (UTI) (urine culture greater than 100,000 cfu/mL) as assessed at Screening (Visit 1). The participant can be rescreened after successful treatment of the UTI (confirmed by a laboratory result of negative urine culture).

• Participant has a neurological cause for detrusor overactivity (e.g., neurogenic bladder, diabetic neuropathy or systemic or central neurological disease such as multiple sclerosis and Parkinson's disease).

• Participant has an indwelling catheter or practices intermittent self-catheterization.

• Participant has a chronic inflammatory condition such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs (i.e., within the confines of the pelvis including the bladder and rectum in both sexes and the uterus, ovaries, and fallopian tubes in females); or of the lower gastrointestinal tract.

• Participant has uncontrolled narrow angle glaucoma, urinary or gastric retention, severe colitis ulcerosa, toxic megacolon, myasthenia gravis, polio or any other medical condition which makes the use of anticholinergics contraindicated.

• Participant has received intravesical injection in the past 12 months with botulinum toxin, resiniferatoxin, or capsaicin.

• Participant has received invasive treatment including electro-stimulation therapy.

• Participant is receiving a bladder training program or pelvic floor exercises which started or has changed less than 30 days prior to Screening.

• Participant has hepatic impairment defined as Child-Pugh Class A, B or C.

• Participant has severe renal impairment defined as creatinine clearance less than 30 mL/min. A participant with End Stage Renal Disease or undergoing dialysis is also not a candidate for the study.

• Participant has severe uncontrolled hypertension, which is defined as a sitting systolic blood pressure greater than or equal 180 mmHg and/or diastolic blood pressure greater than or equal 110 mmHg.

• Participant has evidence of QT prolongation on electrocardiogram (ECG) defined as QTcF greater than 450 msec for males, QTcF greater than 470 msec for females or a known history of QT prolongation.

• Participant has a serum creatinine greater than 150 µmol/L, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2x upper limit of normal (ULN), or γ-GT greater than 3x ULN and considered clinically significant.

• Participant has a hypersensitivity to any components of Myrbetriq (mirabegron), other β-AR agonists, tolterodine or other antimuscarinic agents, or any of the inactive ingredients.

• Participant has been treated with an experimental device within 30 days or received an investigational agent within 30 days prior to Screening.

• Participant has a concurrent malignancy or history of any malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully.

• Participant with current history of alcohol and/or drug abuse.

• Participant is involved in the conduct of the study as an employee of the Astellas group, third party associated with the study, or the study site team.

• Exclusion Criteria assessed at Visit 2 (Week 0):

  • Participant fulfills any exclusion criteria at Visit 1.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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376 participants in 4 patient groups

AB: Mirabegron/Tolterodine ER

Experimental group

Description:

In the treatment sequence AB participants received 25 mg of mirabegron (Myrbetriq) oral controlled absorption system (OCAS) modified-release tablets and 4 mg of placebo-to-match (PTM) tolterodine ER (Detrol LA) orally once a day during period 1. In the period 2, participants received 4 mg of tolterodine ER and 25 mg of PTM mirabegron orally once a day. Four weeks after the start of each 8-week treatment period, 25 mg of mirabegron or mirabegron PTM was increased to 50 mg for the remainder of the treatment period.

Treatment:

Drug: Tolterodine ER

Drug: Mirabegron

BA: Tolterodine ER /Mirabegron

Experimental group

Description:

In the treatment sequence BA participants received 4 mg of tolterodine ER and 25 mg of PTM mirabegron (OCAS) modified-release tablets orally once a day during period 1. In the period 2, participants received 25 mg of mirabegron and 4 mg of PTM tolterodine ER orally once a day. Four weeks after the start of each 8-week treatment period, 25 mg of mirabegron or mirabegron PTM was increased to 50 mg for the remainder of the treatment period.

Treatment:

Drug: Tolterodine ER

Drug: Mirabegron

AA: Mirabegron/Mirabegron

Experimental group

Description:

In treatment sequence AA participants received 25 mg of mirabegron and PTM tolterodine ER 4 mg capsules during period 1 and 2 orally once a day. Four weeks after the start of each 8-week treatment period, 25 mg of mirabegron was increased to 50 mg for the remainder of the treatment period.

Treatment:

Drug: Mirabegron

BB: Tolterodine ER /Tolterodine ER

Experimental group

Description:

Participants received 4 mg of tolterodine ER and PTM mirabegron 25 mg OCAS modified-release tablets orally once a day during period 1 and period 2.

Treatment:

Drug: Tolterodine ER