The following is an excerpt of JALYN® clinical trials information from DailyMed. View full clinical pharmacology information on DailyMed.
A total of 6,975 subjects with mild-to-severe heart failure were evaluated in placebo-controlled trials of carvedilol.The trial supporting the efficacy of JALYN® was a 4‑year multicenter, randomized, double‑blind, parallel‑group trial (CombAT trial) investigating the efficacy of the coadministration of dutasteride 0.5 mg/day and tamsulosin hydrochloride 0.4 mg/day (n = 1,610) compared with dutasteride alone (n = 1,623) or tamsulosin alone (n = 1,611). Subjects were aged at least 50 years with a serum PSA ≥1.5 ng/mL and <10 ng/mL and BPH diagnosed by medical history and physical examination, including enlarged prostate (≥30 cc) and BPH symptoms that were moderate to severe according to the International Prostate Symptom Score (IPSS). Eighty‑eight percent (88%) of the enrolled trial population was white. Approximately 52% of subjects had previous exposure to 5-alpha‑reductase inhibitor or alpha-adrenergic antagonist treatment. Of the 4,844 subjects randomly assigned to receive treatment, 69% of subjects in the coadministration group, 67% in the dutasteride group, and 61% in the tamsulosin group completed 4 years of double‑blind treatment.
Effect on Symptom Score
Symptoms were quantified using the first 7 questions of the International Prostate Symptom Score (IPSS). The baseline score was approximately 16.4 units for each treatment group. Coadministration therapy was statistically superior to each of the monotherapy treatments in decreasing symptom score at Month 24, the primary time point for this endpoint. At Month 24, the mean changes from baseline (±SD) in IPSS total symptom scores were -6.2 (±7.14) for the coadministration group, -4.9 (±6.81) for dutasteride, and -4.3 (±7.01) for tamsulosin, with a mean difference between coadministration and dutasteride of -1.3 units (P<0.001; [95% CI: -1.69, -0.86]), and between coadministration and tamsulosin of -1.8 units (P<0.001; [95% CI: -2.23, -1.40]). A significant difference was seen by Month 9 and continued through Month 48. At Month 48 the mean changes from baseline (±SD) in IPSS total symptom scores were -6.3 (±7.40) for coadministration, -5.3 (±7.14) for dutasteride, and -3.8 (±7.74) for tamsulosin, with a mean difference between coadministration and dutasteride of -0.96 units (P<0.001; [95% CI: -1.40, -0.52]), and between coadministration and tamsulosin of -2.5 units (P<0.001; [95% CI: -2.96, -2.07]). See Figure 1.
Effect on Acute Urinary Retention (AUR) or the Need for BPH-related Surgery
After 4 years of treatment, coadministration therapy with dutasteride and tamsulosin did not provide benefit over dutasteride monotherapy in reducing the incidence of AUR or BPH-related surgery.
In separate 2-year randomized, double-blind trials, compared with placebo, dutasteride monotherapy was associated with a statistically significantly lower incidence of AUR (1.8% for dutasteride versus 4.2% for placebo; 57% reduction in risk) and with a statistically significantly lower incidence of BPH-related surgery (2.2% for dutasteride versus. 4.1% for placebo; 48% reduction in risk).
Effect on Maximum Urine Flow Rate
The baseline Qmax was approximately 10.7 mL/sec for each treatment group. Coadministration therapy was statistically superior to each of the monotherapy treatments in increasing Qmax at Month 24, the primary time point for this endpoint. At Month 24, the mean increases from baseline (±SD) in Qmax were 2.4 (±5.26) mL/sec for coadministration group, 1.9 (±5.10) mL/sec for dutasteride, and 0.9 (±4.57) mL/sec for tamsulosin, with a mean difference between coadministration and dutasteride of 0.5 mL/sec (P = 0.003; [95% CI: 0.17, 0.84]), and between coadministration and tamsulosin of 1.5 mL/sec (P<0.001; [95% CI: 1.19, 1.86]). This difference was seen by Month 6 and continued through Month 24. See Figure 2.
The additional improvement in Qmax of coadministration therapy over dutasteride monotherapy was no longer statistically significant at Month 48.
Effect on Prostate Volume
The mean prostate volume at trial entry was approximately 55 cc. At Month 24, the primary time point for this endpoint, the mean percent changes from baseline (±SD) in prostate volume were -26.9% (±22.57) for coadministration therapy, -28.0% (±24.88) for dutasteride, and 0% (±31.14) for tamsulosin, with a mean difference between coadministration and dutasteride of 1.1% (P = NS; [95% CI: -0.6, 2.8]), and between coadministration and tamsulosin of -26.9% (P<0.001; [95% CI: -28.9, -24.9]). Similar changes were seen at Month 48: -27.3% (±24.91) for coadministration therapy, -28.0% (±25.74) for dutasteride, and +4.6% (±35.45) for tamsulosin.