Xiaflex (collagenase) Treatment Schedule Plan for Peyronie’s Disease
What to expect during a doctor visit?
The doctor will typically measure the penile curvature after injecting the penis with Trimix or PG1 to induce an erection. Men with greater than 30 degree curvature are candidates for Xiaflex. Penile ultrasound may be performed to document plaque.
Xiaflex Treatment Schedule – Peyronie’s disease
Xiaflex Cycle 1:
- Day 1 Cycle 1: Injection of Xiaflex 0.58 mg into the plaque that causes curvature (Injection #1)
- Day 2-4 Cycle 1: Injection of Xiaflex 0.58 mg into the plaque that causes curvature (Injection #2)
- Day 6-8 Cycle 1: Penile remodeling by the treating urologist.
- Weeks 2-7: Patient does penile remodeling himself three times daily
Xiaflex Cycle 2: same as cycle 1 above.
Xiaflex Cycle 3: same as cycle 1 above.
Xiaflex Cycle 4: same as cycle 1 above.
End of Xiaflex Treatment Course for Peyronie’s disease.
What is Penile Remodeling for Treatment of Peyronie’s disease?
The penis was held in this position for 30 seconds. The procedure was repeated 3 times. Subjects were instructed to perform standardized home penile modeling 3 times daily using a similar procedure during the 6-week period between each treatment cycle. Subjects were also advised to gently attempt to straighten the penis without pain during spontaneous erection.
Using the plaque as a fulcrum point, the investigator applied firm, steady pressure to elongate and stretch the penis.
The point of maximal penile curvature was recorded as the distance from the corona to the maximum point of curvature after injecting prostaglandin E1 or trimix into a corpus cavernosum to induce erection. The primary direction of curvature was determined as right or left lateral, dorsolateral or dorsal. Ventral curvature was excluded from analysis. Men were stratified by the degree of the penile curvature abnormality (30 to 60 or 61 to 90 degrees) and randomized to the CCh or placebo group 2:1 in favor of CCh. Investigators were blinded to subject randomization to CCh or placebo and treatments were packaged in visually identical drug kits.
Each treatment cycle included 2 injections of CCh (0.58 mg) or placebo, which were directly injected into the primary plaque at the point of maximal penile curvature abnormality by a standardized injection technique with an interval of approximately 24 to 72 hours between each injection. Approximately 24 to 72 hours after the second injection of each treatment cycle subjects underwent investigator penile plaque modeling. Using the plaque as a fulcrum point, the investigator applied firm, steady pressure to elongate and stretch the penis. The penis was held in this position for 30 seconds. The procedure was repeated 3 times. Subjects were instructed to perform standardized home penile modeling 3 times daily using a similar procedure during the 6-week period between each treatment cycle. Subjects were also advised to gently attempt to straighten the penis without pain during spontaneous erection.
The active placebo group received up to 8 placebo injections (10 mM tris and 60 mM sucrose) and plaque modeling. The treatment cycle was repeated after 6 weeks for up to 4 treatment cycles. After the first treatment cycle, subsequent treatment cycles were not administered if the penile curvature abnormality was reduced to less than 15 degrees or the investigator determined further treatment was not clinically indicated.
The co-primary efficacy end points included the percent improvement from baseline in penile curvature and the change from baseline in the PD symptom bother domain. The percent change in penile curvature from baseline to week 52 vs placebo was assessed using standardized goniometer measurements. The change in the total score of the PD symptom bother domain (4 questions with a total score range of 0 to 16) from baseline to week 52 vs placebo was assessed using the PDQ, which was developed for use in the phase 3 program, as described by the manufacturer (http://www.auxilium.com/PDQ).
Seven secondary efficacy objectives were examined. The proportion of treatment responders was assessed using the global assessment of PD questionnaire. A treatment responder was defined as a subject with a global score of at least 1 (improved in a small but important way). A decrease in the severity of PD psychological and physical symptoms was assessed by the PDQ. These questions refer to the severity of physical symptoms and concerns of men with PD during vaginal intercourse. The change in the IIEF overall satisfaction domain was examined. The percent of composite responders was compared between the groups. Composite responder was defined as a man with 20.0% or greater improvement in penile curvature plus an improvement in the PDQ PD bother score of 1 or greater, or a change from reporting no sexual activity at screening to reporting sexual activity. The remaining secondary efficacy objectives included the change in penile plaque consistency, penile length and the penile pain domain of the PDQ in subjects with a pain score of 4 or greater at baseline screening.
Safety was evaluated by the investigators at all study visits. They examined the incidence of treatment related AEs and the change from baseline in laboratory values and vital signs. Possible treatment related serious AEs, including corporeal rupture and penile hematoma, were included. Immunogenicity was assessed by measuring anti-AUX-I and II antibody levels.