DM-1796 (Gabapentin GR - PHN)

DM-1796 is an investigational formulation of gabapentin, an FDA-approved immediate release pharmaceutical for the treatment of partial epilepsy and management of postherpetic neuralgia (PHN). Depomed is currently developing DM-1796, an AcuForm™-enhanced formulation administered once- or twice-daily for the treatment PHN.

PHN is a persistent neuropathic pain condition. It is caused by nerve damage after a shingles, or herpes zoster, viral infection and afflicts approximately one in five patients diagnosed with shingles (~ 150,000 individuals) in the United States. The incidence of PHN increases in elderly patients, with 75 percent of those over 70 years old who have shingles, developing PHN. The pain associated with PHN reportedly can be so severe that patients are unable to resume normal activities for months.

Leveraging AcuForm Technology

Gabapentin available on the market today is formulated for immediate release (IR). Upon ingestion, the entire administered dose is ‘dumped’ into the stomach allowing for it to be rapidly absorbed into the blood. This rapid absorption leads to peak concentrations of the active ingredient, which gives rise to commonly experienced side effects including dizziness and daytime sleepiness. Patients taking immediate release formulations of gabapentin frequently need to take it four to five times a day to effectively manage their pain.

Formulated with AcuForm delivery technology, DM-1796 is designed for targeted, controlled release to the upper GI tract over a six to eight hour period. This extended release allows for the drug to be gradually absorbed into the blood, reducing the likelihood of peak concentrations and potentially resulting in fewer side effects than seen with immediate release formulations. Greater treatment tolerability and a more convenient dosing regimen made possible with AcuForm could potentially translate into greater patient compliance and ultimately better pain management.

Clinical Results and Development Status

In March 2008, we initiated dosing of the first patient in a Phase 3 clinical trial for DM-1796 for PHN. The study is a randomized, double-blind, placebo-controlled study of approximately 450 PHN patients. Patients in the study are randomized into two treatment arms: placebo, or 1800mg of DM-1796 dosed once daily.

The primary objective of the study is to assess the efficacy of DM-1796 in reducing the pain associated with PHN, measured from baseline pain scores to the end of a ten-week treatment period on the basis of the Likert pain scale. Secondary objectives include an assessment of changes from baseline in sleep interference, and additional patient and clinician assessments of pain and quality of life.

The primary differences in the ongoing study relative to the Phase 3 PHN study we concluded in 2007 are: (a) there is only one active treatment arm (1800 mg once daily) rather than two; and (b) patients enrolled in the study must have “stable PHN disease” for at least six months, rather than three months, following healing of the shingles rash.

In July 2007, Depomed announced results from a Phase 3 clinical trial of DM-1796 for the treatment of PHN.

The randomized, double-blind, placebo-controlled, multi-center trial involved 407 PHN patients. Patients were randomized into one of three treatment groups for ten weeks of treatment: DM-1796 once-daily, DM-1796 twice-daily (each with 1800 mg total daily-dose) and placebo. The primary endpoint of the study was to assess the efficacy of DM-1796 compared to placebo in reducing average daily pain scores from baseline to endpoint. Secondary objectives included generating data on safety, sleep interference and global impressions of changes in pain by investigators and patients.

The primary endpoint was not achieved with statistical significance for either active treatment regimen, as compared to placebo, over the ten-week treatment period. The mean reductions in average daily pain scores from baseline to end of study were 1.83 (once-daily), 1.72 (twice-daily) and 1.43 (placebo). However, statistical significance relative to placebo was achieved in each of the first six weeks for the once-daily treatment arm and in each of the first five weeks for the twice-daily treatment arm. Pain scores in the placebo group continued to improve in the last four weeks of the study.

The secondary endpoints of sleep interference, Clinical Global Impression of Change or CGIC (a scale used by physicians for overall assessment of patient improvement) and Patient Global Impression of Change or PGIC (a scale used by patients to report their overall assessment of change) were all statistically significant for the once-daily treatment compared to placebo over the ten week study period. Sleep interference scores were reduced by 2.01 points with DM-1796 compared to -1.39 with placebo (p=0.014). Physicians reported that 48.0% of patients taking Gabapentin once-daily were "very much improved" or "much improved" compared to 27.1% of the patients who received placebo (p is less than0.001), as measured by the CGIC. Similar results were observed for the PGIC in the once-daily and placebo arms (p=0.009).

The most common side effect observed was dizziness, which is commonly associated with gabapentin. In the trial, the incidence of dizziness for DM-1796 was 10.1% (once-daily) and 14.9% (twice-daily) as compared to 3.0% for placebo. Somnolence was observed in 2.9% of once-daily treated patients and 6.7% of twice-daily treated patients, compared to 2.3% of patients on placebo. Peripheral edema occurred in 5.1% of the once-daily treated population and 4.5% in the twice-daily population compared to no incidents of peripheral edema in the placebo group.

Please visit other pages on this section of the website to learn about DM-1796 in clinical development for the treatment of diabetic peripheral neuropathy and menopausal hot flashes. 

The data referenced in the preceding paragraphs represent the most recently announced data pertaining to this program. For data from earlier trials, please refer to the press release section of this website.