Efficacy and Safety of Desmopressin Melt for the Treatment of Nocturia

Ferring

Status and phase: Completed; Phase 3

Conditions: Nocturia

Treatments: Drug: desmopressin acetate; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00477490

FE992026 CS29

Details and patient eligibility

About

The purpose of this study is to investigate the efficacy and safety of several doses of the melt formulation of desmopressin in a broad population of adult patients with nocturia.

Enrollment: 799 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Written informed consent prior to the performance of any study-related activity.
2. Patients 18 years and older with an average of ≥ 2 nocturnal voids per night as determined by a 3 day frequency-volume chart during the screening period.

Exclusion Criteria:

Males:

1. Clinical suspicion of bladder outlet obstruction and/or urine flow < 5 ml/s. If medical history and/or physical examination suggest bladder outlet obstruction, uroflowmetry should be performed to confirm the diagnosis

2. Surgical treatment for bladder outlet obstruction/benign prostatic hyperplasia performed within the past 6 months

   Females:

3. Pregnancy. Females of reproductive age must have documentation of a reliable method of contraception.

4. Use of pessary for pelvic prolapse.

5. Unexplained pelvic mass.

   Males and Females:

6. Clinical suspicion of urinary retention and/or post void residual volume > 150 ml. If medical history and/or physical examination suggest urinary retention, bladder ultrasound or catheterization should be performed to confirm the diagnosis.

7. Current or past urologic malignancy (e.g., bladder cancer, prostate cancer).

8. Clinical evidence of current genitourinary tract pathology that could interfere with voiding.

9. History of neurogenic detrusor activity (previously known as detrusor hyperreflexia).

10. Suspicion or evidence of cardiac failure.

11. Uncontrolled hypertension.

12. Uncontrolled diabetes mellitus.

13. Renal insufficiency. Serum creatinine must be within normal limits and estimated glomerular filtration rate (eGFR) >=60 mL/min.

14. Active hepatic and/or biliary disease. Aspartate transaminase (AST) or alanine transaminase (ALT) should not be >2 times the upper limit of normal. Total bilirubin should not be > 1.5 mg/dL.

15. Hyponatremia. Serum sodium level must be within normal limits

16. Syndrome of Inappropriate antidiuretic hormone secretion (SIADH).

17. Diabetes insipidus (urine output > 40 ml/kg over 24 hours) as determined by the 3-day voiding diary.

18. Psychogenic or habitual polydipsia

19. Obstructive sleep apnea

    Other

20. Known alcohol or substance abuse

21. Work or lifestyle potentially interfering with regular nighttime sleep (e.g., shift workers)

22. Previous desmopressin treatment for nocturia.

23. Any other medical condition, laboratory abnormality, psychiatric condition, mental incapacity or language barrier that, in the judgment of the investigator, could impair patient participation in the trial.

24. Use of loop diuretics (furosemide, torsemide, ethacrynic acid). Other classes of diuretics (thiazides, triamterene, chlorthalidone, amiloride, indapamide) were permitted, either as monotherapy or combination therapy. Subjects using a diuretic were to be encouraged to take it in the morning, if medically feasible.

25. Use of any other investigational drug within 30 days of screening.

Concomitant Medications

The following medications are permitted provided that the subject has been on a stable dose for the 3 months prior to the screening date (i.e. treatment has not been initiated or discontinued and there has been no change in dose):

• Alpha-blockers: Cardura (doxazosin); Flomax (tamsulosin); Hytrin (terazosin); Uroxatral (alfuzosin)
• 5 alpha-reductase inhibitors: Avodart (dutasteride); Proscar (finasteride)
• Antispasmodic, anticholinergic, antimuscarinic therapy for overactive bladder: Detrol, Detrol LA (tolterodine); Ditropan, Ditropan XL (oxybutynin); Enablex (darifenacin); Levsin(hyoscyamine); Oxytrol transdermal (oxybutynin); Sanctura (trospium); Vesicare (solifenacin)
• Sedative/hypnotic medications for sleep disorders
• Selective serotonin and mixed norepinephrine/serotonin reuptake inhibitors: Celexa (citalopram); Cymbalta (duloxetine); Effexor (venlafaxine); Lexapro (escitalopram); Paxil(paroxetine); Prozac (fluoxetine); Zoloft (sertraline)
• Chronic use of nonsteroidal anti-inflammatory agents
• Diabinese (chlorpropamide)
• Carbamazepine (carbatrol/tegretol)
• Amiodarone

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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799 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants took a placebo 'melt' for 28 days to complete part 1 of the study. In part 2, placebo patients were randomized to one of the other 4 treatment arms based on assignments predetermined at the initial randomization, to receive active desmopressin melt for between 1 and 6 months (until the database for part 1 was locked and treatment was unblinded).

Treatment:

Drug: Placebo

desmopressin melt 10 μg

Experimental group

Description:

Participants took desmopressin melt 10 μg for 28 days to complete part 1 of the study. Participants continued on this dose in part 2 of the study for between 1 and 6 months (until the database for part 1 was locked and treatment was unblinded).

Treatment:

Drug: desmopressin acetate

desmopressin melt 25 μg

Experimental group

Description:

Participants took desmopressin melt 25 μg for 28 days to complete part 1 of the study. Participants continued on this dose in part 2 of the study for between 1 and 6 months (until the database for part 1 was locked and treatment was unblinded).

Treatment:

Drug: desmopressin acetate

desmopressin melt 50 μg

Experimental group

Description:

Participants took desmopressin melt 50 μg for 28 days to complete part 1 of the study. Participants continued on this dose in part 2 of the study for between 1 and 6 months (until the database for part 1 was locked and treatment was unblinded).

Treatment:

Drug: desmopressin acetate

desmopressin melt 100 μg

Experimental group

Description:

Participants will take desmopressin melt 100 μg for 28 days to complete part 1 of the study. Participants will continue on this dose in part 2 of the study for between 1-6 months (until the database for part 1 is locked and treatment is unblinded).

Treatment:

Drug: desmopressin acetate