Paxerol™ for Treatment of Nocturia - A Phase II Placebo-Controlled Trial

NCT02646826 | Completed Phase 2 Results

• 1 other identifier: CL-Paxerol-002
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 4

Brief Summary

This is a multi-center, double-blind, placebo-controlled study with two weeks of daily oral administration of one of three dose levels of Paxerol or placebo in subjects with nocturia. Eligible study subjects will be identified according to inclusion/exclusion criteria (see below), and baseline assessments will be recorded. Due to small sample size of 25 patients per group in this proof-of-principle dosing-finding trial, stratification according to gender and BMI will be difficult. However, similar distribution of patient types to the four treatment groups will be attempted by evenly assigning patients to the four treatment groups according to genders and body mass index (BMI) of \<25, 25-30 and 30-40. Paxerol or placebo will be taken 30 minutes before bedtime daily for two weeks. Nocturia frequency, Nocturia Quality of Life (NQOL), Duration of First Undisturbed Sleep (DFUS), total hours of nightly sleep, safety and tolerability will be monitored before and after a two-week treatment period. Results from subjects treated with different doses of Paxerol and placebo will be assessed and compared. Baseline urinary Prostaglandin E2 (PGE2) production will also be assayed to assess potential correlation between baseline urinary PGE2 production and responsiveness to Paxerol treatment.

Conditions

Nocturia

Outcome Measures

Primary Outcomes (2)

• Change in Nocturia Episodes

  Change in number of nocturia episodes associated with one of three dose levels of Paxerol vs. placebo is assessed during the 2-week treatment period.

  Up to 2 weeks

• Clinical Benefit Based on Nocturia Quality of Life (NQOL).

  The degree of clinical benefit, via NQOL, associated with one of three dose levels of Paxerol vs. placebo is assessed after the 2-week treatment period. This is on a scale of 0 to 100, with 0 being the best score.

  Up to 2 weeks

Secondary Outcomes (2)

• Duration of First Undisturbed Sleep (DFUS)

  Up to 2 weeks

• Total Hours of Nightly Sleep

  Up to 2 weeks

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Subjects are treated with placebo tablets.

Other: Placebo

Paxerol - Dose Level 1

EXPERIMENTAL

Subjects are treated with the first dose level of Paxerol.

Drug: Paxerol - Dose Level 1

Paxerol - Dose Level 2

EXPERIMENTAL

Subjects are treated with the second dose level of Paxerol.

Drug: Paxerol - Dose Level 2

Paxerol - Dose Level 3

EXPERIMENTAL

Subjects are treated with the third dose level of Paxerol.

Drug: Paxerol - Dose Level 3

Interventions

Placebo OTHER

Subjects are treated with Placebo tablets

Also known as: Placebo control

Placebo

Paxerol - Dose Level 1 DRUG

Subjects are treated with the first dose level of Paxerol

Also known as: Treatment arm 1

Paxerol - Dose Level 1

Paxerol - Dose Level 2 DRUG

Subjects are treated with the second dose level of Paxerol

Also known as: Treatment arm 2

Paxerol - Dose Level 2

Paxerol - Dose Level 3 DRUG

Subjects are treated with the third dose level of Paxerol

Also known as: Treatment arm 3

Paxerol - Dose Level 3

Eligibility Criteria

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

You may qualify if:

• Subjects diagnosed with nocturia, as defined by International Continence Society (i.e., the interruption of sleep one or more times at night to void), confirmed by evaluation in participating investigator's urology practice for the following characteristics: nocturia is related to overactive bladder (OAB); nightly ≥2.5 times nocturia present for at least 3 months and not considered caused by persistent or recurrent urinary tract infection; Post-Void Residual (PVR) urine volume must be \<80 cc at the time of screening; did not respond well to, or unwilling to have, lifestyle modification, behavioral and conservative therapies, such as dietary changes, timed voiding, urge suppression (e.g., pelvic floor exercises \[PFE\] at the time of urge episodes), biofeedback, etc.
• Males or females, ≥18 years of age with Body Mass Index (BMI) \<40.
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device \[IUD\], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation.
• Ability to understand and sign the study Informed Consent Form (ICF), communicate with the investigators, and understand and comply with the requirements of the protocol, including completion of participation in all phases of the study.
• No current or medical history of gastrointestinal bleeding or malformation; bleeding diathesis; or restless leg syndrome.
• Not using within 4 weeks before study initiation, or anticipating the use during the study, of the following drugs: antiplatelet or anticoagulant drugs; any Selective Serotonin Re-uptake Inhibitors (SSRIs) or anti-diuretic medications; or warfarin
• Resting heart rate between 55 and 100 beats per minute, inclusive of both.

You may not qualify if:

• Pregnant or nursing women.
• Known presence of urinary tract infection (UTI) within 4 weeks before study initiation
• Known sleep interruptions due to sleep apnea, dyspepsia or other gastro-intestinal symptoms, seizure disorders or other neurologic symptoms
• Allergy to or intolerance of acetaminophen, ibuprofen, or any inactive component of the study drug formulations.
• A history of allergy to aspirin or other NSAIDs.
• Congenital or acquired structural abnormality of the genitourinary tract.
• Prostate cancer of any stage that has required any treatment.
• Any neurodegenerative disease (including but not limited to Parkinson's Disease, Alzheimer's Disease, Amyotrophic Lateral Sclerosis, Pick's Disease, Multi-Infarct Dementia or recent history of head trauma associated with concussion, stroke or serious cerebrovascular events) which may indicate problems in providing consistent and reliable Patient-Reported Outcomes (PRO) such as diary, Quality-of-Life, etc. required in this study.
• Uncontrolled hypertension (blood pressure \>150/100 mm Hg).
• Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, or New York Heart Association Class II, III or IV), severe debilitating pulmonary disease, or history of stroke (hemorrhagic or thrombotic), A-V malformation, or other cerebrovascular disease.
• Receipt of any investigational drug or participation in any clinical trial within 30 days prior to study participation.
• Use of acetaminophen, ibuprofen, acetylsalicylic acid (ASA) or any NSAID on the day of entry into the study or any anticipated use during the study. In the event of the need for any unanticipated use of such drugs during the trial, the timing and doses of such use should be carefully recorded and reported at the next visit to the clinic.
• Any medical problem requiring uninterrupted use of acetaminophen, ibuprofen, or any NSAIDs, or any other pain medication.
• Daily use of phosphodiesterase (PDE) inhibitors (such as sildenafil, tadalafil, vardenafil, avanafil, and udenafil) within 30 days prior to study or any anticipated daily use during the study. (Note: PDE inhibitors are known to have positive effect on voiding dysfunction and thus can interfere with the assessment of Paxerol \[Ückert et al 2010\].)
• History of polyuria or evidence of polyuria (estimation of daily production \>2.5 liters of urine).

Sponsors & Collaborators

• Wellesley Pharmaceuticals, LLC: lead

Study Sites (4)

A and I Medical P.C.

Brooklyn, New York, 11229, United States

Location

The Westchester Medical Group PC

Harrison, New York, 10604, United States

Location

Dr. George Klein

New York, New York, 10021, United States

Location

Washington High Urology

New York, New York, 10032, United States

Location

Related Publications (1)

• Lee KC, Rauscher F, Kaminesky J, Ryndin I, Xie L, Zhao Y, Khusid JA, Weiss JP. Novel immediate/sustained-release formulation of acetaminophen-ibuprofen combination (Paxerol(R)) for severe nocturia associated with overactive bladder: A multi-center, randomized, double blinded, placebo-controlled, 4-arm trial. Neurourol Urodyn. 2019 Feb;38(2):740-748. doi: 10.1002/nau.23910. Epub 2018 Dec 28.

  PMID: 30592553 DERIVED

MeSH Terms

Conditions

Nocturia

Condition Hierarchy (Ancestors)

Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

None of the adverse events were considered to be drug related.

Results Point of Contact

• Title: David Dill
• Organization: Wellesley Pharmaceuticals, LLC

ddill@wellesleypharma.com

2154930168

Study Officials

• David A Dill

  Wellesley Pharmaceuticals

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2015
• First Posted: January 6, 2016
• Study Start: January 1, 2016
• Primary Completion: October 1, 2017
• Study Completion: November 1, 2017
• Last Updated: June 14, 2019
• Results First Posted: June 14, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)