Hythiam Announces Results of Two Double-Blind, Placebo-Controlled Studies on Impact of PROMETA Treatment Program for Alcohol Dependence
Statistical Significance Achieved for Key Measures in Each Study
LOS ANGELES--(BUSINESS WIRE)--Mar 31, 2009 -Hythiam, Inc. (NASDAQ: HYTM) announced the final results of two double-blind, placebo-controlled studies that help complete the Company's data set on the impact of the PROMETA® Treatment Program (PROMETA) on alcohol dependent subjects. The first set of results includes data from the full 14-week double-blind, placebo-controlled study conducted by leading alcoholism expert Raymond Anton, M.D., of Medical University of South Carolina. Initial 6-week topline results were released by Dr. Anton at the RSA conference held in Washington, D.C. in June 2008. At weeks 6 and 14, the data demonstrated statistical significance for key endpoints for subjects with greater symptoms of withdrawal as measured by higher Clinical Institute Withdrawal Assessment (CIWA) scores, when compared to lower-CIWA patients. Also, at week 6, the higher-CIWA PROMETA subjects achieved statistical significance for percent days abstinent when compared to placebo, and at week 14 the higher-CIWA PROMETA subjects continued to be superior for end points that included percent days abstinent and craving when compared to placebo. The second set of results includes data from an 8-week, double-blind, placebo-controlled study on alcohol dependent subjects, all with low CIWA scores, that was recently completed by Joseph Volpicelli, M.D., Ph.D. at the Institute of Addiction Medicine. Results from this study demonstrated that, for lower-CIWA subjects with a clinical history of alcohol withdrawal symptoms, the PROMETA group experienced statistically significant decreases in alcohol craving and alcohol consumption, as compared to placebo. In addition, across the entire intent-to-treat sample, differences favored the PROMETA group.
Given the industry pressure to reduce health care costs and because of rising alcoholism rates due to the current economic environment, health plans are seeking cost effective solutions to address these issues, and recent results from Dr. Anton's and Dr. Volpicelli's data sets should help drive adoption of the Company's CatasysTM Offering.
The study data from Dr. Anton's higher-CIWA PROMETA subjects and Dr. Volpicelli's lower-CIWA PROMETA subjects with a history of alcohol withdrawal, provides clinicians with a guide as to the most effective time to use PROMETA on alcohol dependent patients. Rapid reduction in craving may lead to improved treatment engagement and a higher retention rate because craving, particularly during the initial treatment period, has been reported in the literature to be predictive of relapse. In one study in particular, data showed that craving predicts drinking during treatment, and even more accurately than prior drinking habits.1 In addition, previously conducted research demonstrated that PROMETA significantly reduced drinking in subjects experiencing higher levels of alcohol withdrawal symptoms.
The final results from both studies are significant for the Company's Catasys managed care offering, which is aimed at the more costly patients who are frequent high-utilizers of health plan services. The studies demonstrate that pharmacologic intervention has a significant impact on those who have withdrawal symptoms or a history of withdrawal symptoms, indicating they may benefit even further from Catasys, which is an integrated substance dependence program that combines medical and psychosocial components in an outpatient setting, and includes long term coaching aimed at achieving treatment compliance and preventing relapse for substance dependent patients.
“We are pleased that Dr. Anton demonstrated the durability of the results experienced by the higher-CIWA group at the conclusion of the 14 week study,” said Hythiam's Senior Vice President of Scientific Affairs, Dr. Gary Ingenito. “Although we didn't receive clarity on the lower-CIWA group in Dr. Anton's study, Dr. Volpicelli's study was much larger, involving 117 lower-CIWA subjects, and it demonstrated that the PROMETA group had better clinical outcomes and achieved statistical significance during the active treatment period among subjects with a history of alcohol withdrawal symptoms. The rapid reduction in craving for the lower-CIWA PROMETA subjects in Dr. Volpicelli's study and the maintained reduction for the higher-CIWA PROMETA subjects in Dr. Anton's study suggest that PROMETA may be useful in reducing a barrier to patient engagement in an ongoing psychosocial program, and improve the chances of remaining in treatment. The results from the data of both studies are consistent with pre-clinical research and data from other PROMETA studies. Together they provide significant depth and clarity to guide clinicians in the most effective time to use PROMETA in alcohol dependent patients. We now have a more complete clinical picture of the impact of PROMETA on alcohol dependent patients, and look forward to publication of final results from both studies in peer-reviewed journals.”
Results from the end of the 8-week follow-up period of Dr. Anton's 14-week study maintained significance for key endpoints. At week 14, subjects with greater symptoms of withdrawal as measured by higher-CIWA scores, achieved statistical significance in percent days abstinent when compared to those with lower CIWA scores (p=.05). CIWA scores are based on a 67-point scale, and are a point-in-time assessment of withdrawal symptoms. The scores are typically used as a measure to guide the appropriate level of care and type of treatment. Although not statistically significant, results also favored higher-CIWA PROMETA subjects, as compared to placebo, in percent days abstinent, craving, percent heavy drinking days, and drinks per day. Additional week 14 results also demonstrated that these higher-CIWA subjects maintained statistical significance in other measures that included craving and the obsessive compulsive drinking scale (p=.03), as compared to lower-CIWA subjects.
The 14-week study, over a 6 week treatment phase and an 8 week follow up phase, was designed to evaluate the impact of PROMETA on percent days abstinent, other use measures and cravings. Alcoholic subjects were stratified into 2 groups upon enrollment: those with higher alcohol withdrawal, as defined by their CIWA scores, and those with lower-CIWA scores. Subjects were not required to maintain prior abstinence.
For the lower-CIWA group in Dr. Anton's study, PROMETA had no effect or a lesser response compared to placebo subjects, who fared better in the study. Additional analysis of these results across the 14-week study, as well as final review of other study procedures, including functional MRI and acoustic startle, provided no additional clarity on the lower-CIWA outcomes. However, Dr. Volpicelli conducted a larger, 117-subject, 8-week, double-blind, placebo-controlled study on alcohol dependent subjects with low CIWA scores, utilizing 3 infusions versus the 2 used in Dr. Anton's study. Dr. Volpicelli's study evaluated efficacy and tolerability of the medical intervention of the PROMETA Treatment Program in alcohol dependent subjects with lower CIWA scores following alcohol detoxification. This second set of results from Dr. Volpicelli demonstrated that for lower-CIWA subjects with a clinical history of alcohol withdrawal symptoms, the PROMETA group experienced statistically significant decreases in alcohol craving and alcohol consumption, as compared to placebo. Across the entire intent-to-treat sample, differences favored the PROMETA group. The group of subjects with a reported history of previous alcohol withdrawal symptoms composed two-thirds of the entire study sample. For this group of subjects, percent drinking days and alcohol craving showed statistically significant group differences during the study's active treatment phase. Dr. Volpicelli's study is the first to extend these results to subjects who are not in withdrawal at the time of randomization, but have a history of withdrawal symptoms.
Subjects were included in Dr. Volpicelli's study following successful completion of alcohol detoxification and had abstained from alcohol for at least three days, and exhibited few withdrawal symptoms. The severity of withdrawal was assessed by the CIWA scale. The study enrolled 117 male and female subjects into the 8-week trial. The first 4 weeks comprised the active treatment phase of the study and the subsequent 4 weeks contained the follow-up phase. A total of 3 infusions of flumazenil were given during the first week of treatment along with 38 days of oral gabapentin. In addition, the Institute of Addiction Medicine used its BRENDA program for psychosocial support, which was intended to enhance motivation and medication compliance. The study's overall retention rate was 79%.
Alcohol craving as measured by the Penn Alcohol Craving Scale was significantly reduced in the PROMETA group, by 39% from pre-infusion status to end of the active treatment phase compared to a 14% decrease in the placebo group (p=0.02). These differences were no longer statistically significant by the end of the follow-up period, but the PROMETA group remained numerically superior to placebo in decreasing cravings with a reduction of 37% compared to 32% for placebo. The results were more dramatic for the group of subjects with a history of alcohol withdrawal with a 45% reduction for the PROMETA group, compared to a 30% reduction for placebo from pre-infusion status to the end of the active treatment phase (p=.02). Overall, PROMETA decreased the craving score more rapidly than placebo, and only over time did the placebo group slowly decline.
The percent drinking days for all study participants was not statistically different between the groups, although the PROMETA group was numerically better than placebo in reducing the percent of drinking days from baseline throughout the 8-week study. At the end of the active treatment phase, the PROMETA group had reduced percent of drinking days by 67% versus placebo at 56%; during the subsequent follow-up period, PROMETA reduced percent of drinking days by 63% versus placebo at 54%; and overall the PROMETA group had 65% fewer drinking days compared to 55% with placebo. Similarly, when examining time to first drink and time to first heavy drinking day, the PROMETA group took more time to reach the event than the placebo group, but this difference was not statistically significant. Over the 8 week study, 31% of the PROMETA group was abstinent versus 21% in the placebo group.
For the subjects who reported a history of having previously experienced alcohol withdrawal symptoms, group differences emerged during the active treatment phase. An analysis of this subgroup revealed a statistically significant difference in percent drinking days at end of the active treatment phase of the study, favoring the PROMETA group; 12% drinking days for PROMETA versus 22% drinking days for placebo (p=0.02). This represents a 46% reduction in drinking days for the PROMETA group compared to placebo. The statistical significance abated during the follow-up phase of the study. Across the entire 8 weeks, the PROMETA group was numerically superior and had fewer percent drinking days (16%) versus placebo (21%). These results suggest that individuals who have previously experienced withdrawal symptoms may experience a greater benefit from PROMETA.
|1.||Flannery B.A., Poole S.A., Gallop R.J. and Volpicelli J.R., Alcohol Craving Predicts Drinking During Treatment: An Analysis of Three Assessment Instruments. Journal of Studies on Alcohol. 2003; 120-126.
Hythiam's PROMETA Treatment Program is designed for use by health care providers seeking to treat individuals diagnosed with dependencies to alcohol, cocaine or methamphetamine, as well as combinations of these drugs. The PROMETA Treatment Program includes nutritional supplements, FDA-approved oral and IV medications used off-label and separately administered in a unique dosing algorithm, as well as psychosocial or other recovery-oriented therapy chosen by the patient and his or her treatment provider. As a result, PROMETA represents an innovative approach to managing alcohol, cocaine, or methamphetamine dependence that is designed to address physiological, nutritional, and psychosocial aspects of the disease, and is thereby intended to offer patients an opportunity to achieve sustained recovery. To learn more, please visit www.prometainfo.com.
Hythiam, Inc. provides through its CatasysTM offering, behavioral health management services to health plans, employers and unions through a network of licensed and company managed healthcare providers. The Catasys substance dependence program is built around medical and psychosocial interventions, including the patented PROMETA® Treatment Program for alcoholism and stimulant dependence. The PROMETA Treatment Program, which integrates behavioral, nutritional, and medical components, is also available on a private-pay basis through licensed treatment providers and company managed treatment centers. Hythiam does not practice medicine or manufacture, distribute, or sell any medications and has no relationship with any manufacturers or distributors of medications used in the PROMETA Treatment Program. For further information, please visit www.hythiam.com.
Except for statements of historical fact, the matters discussed in this press release are forward looking and made pursuant to the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect numerous assumptions and involve a variety of risks and uncertainties, many of which are beyond the company's control that may cause actual results to differ materially from stated expectations. These risk factors include, among others, limited operating history and lack of statistically significant formal research studies, the risk that treatment protocols might not be effective, difficulty in developing, exploiting and protecting proprietary technologies, intense competition and substantial regulation in the healthcare industry; and additional risks factors as discussed in the reports filed by the company with the Securities and Exchange Commission, which are available on its website at http://www.sec.gov.
Contact: Investor Relations:
Stacey Stockhaus, 310-444-4333
Posted: April 2009