Pfizer Inc. (NYSE:PFE) announced today top-line results from a
double-blind Phase 3 study evaluating pregabalin controlled-release (CR)
formulation in adult patients with postherpetic neuralgia (pain after
shingles or PHN). The results show that pregabalin CR resulted in a
statistically significant positive effect compared to placebo in the
primary endpoint, time to loss of therapeutic response (LTR) in pain
reduction. PHN is a type of peripheral neuropathic pain caused by nerve
damage. Symptoms include continued burning or electric shock-like pain.1
This study is the final of three Phase 3 studies of the pregabalin CR
formulation conducted to ascertain the potential use of pregabalin as a
once-a-day therapy. The first study in adults with partial onset
seizures with epilepsy did not meet its primary endpoint. In the second
study in patients with fibromyalgia, pregabalin CR had a statistically
significant positive effect compared to placebo in the primary endpoint,
time to LTR in pain reduction.
About the Study
The objective of the Phase 3 double-blind, randomized,
placebo-controlled study was to evaluate the safety and efficacy of
pregabalin CR compared with placebo in the durability of effect for the
treatment of pain associated with PHN among patients who initially
respond to single-blind pregabalin.
The study was composed of 4 phases: baseline (1 week), single-blind
treatment (6 weeks), double-blind treatment (13 weeks), and a 1-week
double-blind taper. During the single-blind phase, there were two
stratification groups receiving different doses of pregabalin. Patients
with normal renal function received a dose between 165 mg/day to 660
mg/day while patients with low renal function received between 82.5
mg/day and 330 mg/day of pregabalin. In the double-blind phase, patients
were randomized to continued pregabalin CR treatment at the optimized
dose or to matching placebo.
A total of 796 subjects were enrolled into the single-blind phase from
116 sites in 17 countries. Of the 796 subjects, 418 (51.8%) completed
the single-blind phase, had ≥50% pain response (i.e., ≥50% reduction in
pain compared to baseline) and were randomized into double-blind phase.
The primary endpoint, defined as the time to LTR during the double-blind
phase (LTR; <30% pain response relative to the baseline mean pain or
withdrawal due to lack of efficacy or adverse events), occurred in 29 of
208 (13.9%) patients in the pregabalin group as compared with 63 of 205
(30.7%) subjects in the placebo group. The difference between the
treatments was statistically significant.
Pregabalin CR was well tolerated and the safety profile was consistent
with the known profile for pregabalin (immediate release) in PHN
patients. The most common adverse events with pregabalin CR were
dizziness, somnolence, peripheral edema and weight increase.
Full results from the study will be submitted for publication when
analyses are complete.
About Lyrica
Lyrica® is currently approved for various indications in 120
countries and regions globally.
Lyrica is approved for five indications in the U.S., of which four are
in the therapeutic area of pain. These indications include neuropathic
pain associated with diabetic peripheral neuropathy, post-herpetic
neuralgia (pain after shingles), neuropathic pain associated with spinal
cord injury, fibromyalgia and partial onset seizures in adults with
epilepsy who take one or more drugs for seizures.
Lyrica’s ongoing clinical development program is focused on the
significant unmet needs of patients with certain chronic pain conditions.
Antiepileptic drugs (AEDs), including Lyrica, increase the risk of
suicidal thoughts or behavior in patients taking AEDs for any
indication. There have been post-marketing reports of angioedema and
hypersensitivity with Lyrica. Treatment with Lyrica may cause dizziness,
somnolence, dry mouth, edema and blurred vision. Other most common
adverse reactions include weight gain, constipation, euphoric mood,
balance disorder, increased appetite and thinking abnormal (primarily
difficulty with concentration/attention).
For Lyrica prescribing information in the U.S. visit www.lyrica.com.
Important Safety Information
LYRICA is contraindicated in patients with known hypersensitivity to
pregabalin or any of its other components. Angioedema and
hypersensitivity reactions have occurred in patients receiving
pregabalin therapy.
There have been postmarketing reports of hypersensitivity in patients
shortly after initiation of treatment with LYRICA. Adverse reactions
included skin redness, blisters, hives, rash, dyspnea, and wheezing.
Discontinue LYRICA immediately in patients with these symptoms.
There have been postmarketing reports of angioedema in patients during
initial and chronic treatment with LYRICA. Specific symptoms included
swelling of the face, mouth (tongue, lips, and gums), and neck (throat
and larynx). There were reports of life-threatening angioedema with
respiratory compromise requiring emergency treatment. Discontinue LYRICA
immediately in patients with these symptoms.
Antiepileptic drugs (AEDs) including LYRICA increase the risk of
suicidal thoughts or behavior in patients taking AEDs for any
indication. Monitor patients treated with any AED for any indication for
the emergence or worsening of depression, suicidal thoughts or behavior,
and/or any unusual changes in mood or behavior. Pooled analyses showed
clinical trial patients taking an AED had approximately twice the risk
of suicidal thoughts or behavior than placebo treated patients. The
estimated incidence rate of suicidal behavior or ideation among 27,863
AED-treated patients was 0.43%, compared to 0.24% among 16,029
placebo-treated patients, representing an increase of approximately one
patient for every 530 patients treated with an AED.
The most common adverse reactions across all LYRICA clinical trials are
dizziness, somnolence, dry mouth, edema, blurred vision, weight gain,
constipation, euphoric mood, balance disorder, increased appetite, and
thinking abnormal (primarily difficulty with concentration/attention).
Inform patients taking LYRICA that dizziness and somnolence may impair
their ability to perform potentially hazardous tasks such as driving or
operating complex machinery until they have sufficient experience with
LYRICA to determine its effect on cognitive and motor function.
In controlled studies, a higher proportion of patients treated with
LYRICA reported blurred vision (7%) than did patients treated with
placebo (2%), which resolved in a majority of cases with continued
dosing. Consider more frequent assessment for patients who are already
routinely monitored for ocular conditions.
Higher frequency of weight gain and edema was observed in patients
taking both LYRICA and thiazolidinedione antidiabetic drugs. Exercise
caution when coadministering these drugs. Patients who are taking other
drugs associated with angioedema such as angiotensin converting enzyme
inhibitors (ACE- inhibitors) may be at increased risk of developing
angioedema. Exercise caution when using LYRICA in patients who have had
a previous episode of angioedema.
LYRICA may exacerbate the effects of oxycodone, lorazepam, or ethanol on
cognitive and gross motor functioning.
Patients with a history of drug or alcohol abuse may have a higher
chance of misuse or abuse of LYRICA.
Withdraw LYRICA gradually over a minimum of 1 week. Discontinue LYRICA
immediately in patients with symptoms of hypersensitivity or angioedema.
Patients with a creatinine clearance of 30 to 60 mL/min had a greater
incidence of discontinuation due to adverse reactions than patients with
normal creatinine clearance. Adjust the daily dose of LYRICA for
patients with reduced renal function (creatinine clearance ≤60 mL/min)
and in those undergoing hemodialysis. Administer a supplemental dose of
LYRICA immediately following every 4-hour hemodialysis treatment.
In standard, preclinical in vivo lifetime carcinogenicity studies of
LYRICA, an unexpectedly high incidence of hemangiosarcoma was identified
in 2 different strains of mice. The clinical significance of this
finding is unknown. In clinical studies across various patient
populations comprising 6396 patient-years of exposure in patients >12
years of age, new or worsening preexisting tumors were reported in 57
patients.
Please see full LYRICA prescribing information at www.LYRICA.com.
Pfizer Inc.: Working together for a healthier world®
At Pfizer, we apply science and our global resources to bring therapies
to people that extend and significantly improve their lives. We strive
to set the standard for quality, safety and value in the discovery,
development and manufacture of health care products. Our global
portfolio includes medicines and vaccines as well as many of the world's
best-known consumer health care products. Every day, Pfizer colleagues
work across developed and emerging markets to advance wellness,
prevention, treatments and cures that challenge the most feared diseases
of our time. Consistent with our responsibility as one of the world's
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more than 150 years, Pfizer has worked to make a difference for all who
rely on us. To learn more, please visit us at www.pfizer.com.
DISCLOSURE NOTICE: The information contained in this release is as of
December 18, 2014. Pfizer assumes no obligation to update
forward-looking statements contained in this release as the result of
new information or future events or developments.
This release contains forward-looking information about a potential
additional indication for Lyrica as a once-a-day treatment, including
its potential benefits, that involves substantial risks and
uncertainties that could cause actual results to differ materially from
those expressed or implied by such statements. Risks and
uncertainties include, among other things, the uncertainties inherent in
research and development; whether and when any new drug applications may
be filed in any jurisdictions for such additional indication for Lyrica;
whether and when regulatory authorities in such jurisdictions will
approve any such applications, which will depend on the assessment by
such regulatory authorities of the benefit-risk profile suggested by the
totality of the efficacy and safety information submitted; decisions by
regulatory authorities regarding labeling and other matters that could
affect the availability or commercial potential of such additional
indication for Lyrica; and competitive developments.
A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended December
31, 2013 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned “Risk Factors” and “Forward-Looking
Information That May Affect Future Results,” as well as in its
subsequent reports on Form 8-K, all of which are filed with the SEC and
available at www.sec.gov
and www.pfizer.com.
1 UCSF Medical Center. Post-Herpetic Neuralgia. Last accessed
at http://www.ucsfhealth.org/conditions/post-herpetic_neuralgia/.
on 25 July 2014.
Copyright Business Wire 2014