Treatment goals for PD are curvature reduction,
improved sexual function and a decrease in other
reported PD specific symptoms.
Results from this
phase 2b study revealed significant improvements
in penile curvature and PD symptom bother scores
with CCh treatment compared with placebo. The
safety results of this study indicate that CCh is well
tolerated with TEAEs or treatment related AEs that
were at most mild or moderate in severity and usu-
ally resolved without intervention.
There has been significant variability in study
design and lack of consistency in measuring and
interpreting outcomes in many PD series.
objective measurements such as penile curvature
and length, etc, are difficult to make consistently
and there is operator dependent variation. To help
decrease variability penile curvature measurements
were standardized by cavernous injection of prosta-
glandin E1 to pharmacologically induce erection be-
fore measurement. However, since a fixed dose of
prostaglandin E1 was used, all subjects may not
have responded optimally, which could have been a
limiting factor. Also, investigators may have experi-
enced a brief learning curve with the injection tech-
nique, which may have affected the consistency of
Physical and psychological symptoms associated
with PD should be considered when selecting a ther-
apeutic regimen. However, the lack of a standard
survey to assess PD specific symptoms was noted by
many experts, resulting in subsequent development
of the PD-PRO.
Data on the psychological impact of
PD shows that a significant number of patients pres-
ent with clinically meaningful depression, sometimes
severe emotional distress and low self-esteem.
Questions in the PD symptom bother domain of the
PD-PRO were designed to measure how bothered the
subject is by PD symptoms. Significant positive results
were observed after CCh treatment.
The goal of surgical correction of PD is to focally
improve the expansion of scarred tunica albuginea.
Intralesional injections of CCh enzymatically weaken
the plaque, which in conjunction with penile model-
ing may accomplish the same goal. In this study the
investigator modeled the flaccid penis in select pa-
tients. There was greater mean percent improve-
ment in penile curvature in those who underwent
physician modeling compared to the improvement in
penile curvature in those without modeling (32.4%
vs 27.1%) with no apparent increased risk to the
patient. Although the difference was not statisti-
cally significant, greater mean improvement was ob-
served with physician modeling.
Since spontaneous improvement in PD symptoms
is rare,
an unexpected study result was the high
placebo response in the group without modeling.
There was an imbalance among the groups in dis-
ease duration. The placebo group without modeling
had a higher percent of patients with a shorter dis-
ease history than any of the other groups. Possibly
some of these patients had not attained a steady state
of disease, resulting in spontaneous reduction of defor-
mity, which may have confounded the results. Due to
this imbalance and the few patients in the placebo
groups due to 3:1 randomization it is difficult to
determine the relevance of the higher than expected
placebo response.
CCh treatment provides significant improvement in
penile curvature and in the PD symptom bother
domain. CCh was well tolerated with no treatment
related SAEs. Results suggest that CCh should be
considered a viable treatment option for patients
with PD. Placebo controlled, phase 3 studies of PD
(NCT01221623 and NCT01221597) are currently
ongoing to provide additional safety and efficacy in-
Dr. Jennifer Kent, MedVal Scientific Information
Services, assisted with the manuscript.
Study Population Inclusion and Exclusion Criteria
Inclusion Criteria
Healthy, heterosexual males over age 18 in a stable relationship with a partner/spouse (for at least 3 months)
Diagnosis of PD for at least 6 months
Penile curvature of at least 30 degrees in the dorsal, lateral or dorsal/lateral plane (must have been possible to delineate the single plane of maximal curvature for
Functional difficulty related to PD (eg ED or difficulty with intromission)
Signed informed institutional review board approved consent agreement
Exclusion Criteria
Penile curvature of less than 30 or greater than 90 degrees
Calcified plaque as evident by appropriate radiographic evaluation, penile X-ray or penile ultrasound (noncontiguous stippling was allowed)
Isolated hourglass malformation of the penis without curvature
Plaque causing curvature of the penis located proximal to the base of the penis (injection of the local anesthesia would have interfered with the injection of CCH into
the plaque)