RxPG News : PPI

Immediate-release Omeprazole Significantly Reduces Nocturnal Acidity

Wed, 15 Jun 2005 00:14:38 PST

( from http://www.rxpgnews.com ) Santarus, Inc. (NASDAQ:SNTS), a specialty pharmaceutical company focused on therapies for gastrointestinal diseases and disorders, today announced the publication of clinical trial results in the June 15, 2005 issue of Alimentary Pharmacology & Therapeutics, a peer-reviewed gastroenterology journal.

The trial results showed that immediate-release ZEGERID(R) (omeprazole) Powder for Oral Suspension 40 mg significantly reduced gastric acidity throughout the night compared to Protonix(R) (pantoprazole) Delayed-Release Tablets 40 mg when dosed once a day in the evening. Both drugs are proton pump inhibitors (PPIs) used to reduce gastric acid and treat symptoms of gastroesophageal reflux disease (GERD).

"ZEGERID's effectiveness in controlling nocturnal gastric acidity when dosed at bedtime is intriguing and worthy of further study," said Donald Castell, MD, lead author on the article. "The goal of PPI use in the evening is to reduce nocturnal gastric acidity, which reduces the possibility of acid reflux in patients with GERD," Dr. Castell added. Dr. Castell is professor of medicine and director, Esophageal Disorders Program at the Medical University of South Carolina, and is past president of the American Gastroenterological Association.

In this study, 36 patients with nighttime symptoms of GERD participated in an open-label, randomized crossover trial. The patients received repeated evening doses of either ZEGERID or Protonix for one week, followed by twice-daily dosing for one day. After a washout period, patients were treated with the alternative drug, following the same schedule.

During once-daily dosing, ZEGERID was administered at bedtime; however, reflecting current practice for evening dosing of delayed-release PPIs, Protonix was administered before dinner. During twice-daily dosing, both drugs were administered before breakfast and at bedtime. The protocol allowed 18 patients to return for additional once-daily dosing of ZEGERID 40 mg on six consecutive days, with 24-hour pH monitoring beginning at the last dose. Gastric acidity was calculated separately over an 8-hour nighttime interval and over 24 hours.

Measurements included median gastric pH, percentage of time gastric pH was greater than 4 and percentage of patients with nocturnal acid breakthrough (NAB), defined as the occurrence of continuous gastric pH of less than 4 for more than one hour during the night while receiving PPI therapy. The amount of time that pH is greater than 4 is a parameter frequently used to evaluate the clinical effects of treatment with PPIs in patients with acid-related diseases.

Data from 32 patients were available for analysis. After repeated once-daily dosing, ZEGERID 40 mg produced significantly better nocturnal gastric acid control than Protonix 40 mg: median gastric pH was 4.7 vs. 2.0; the time with gastric pH greater than 4 was 55 percent vs. 27 percent; and patients with NAB totaled 53 percent vs. 78 percent (P less than or equal to 0.005 for all comparisons). After twice-daily dosing of ZEGERID 40 mg and Protonix 40 mg, respectively: median gastric pH was 6.5 vs. 1.5; the time with gastric pH greater than 4 was 92 percent vs. 37 percent; and patients with NAB totaled 12 percent vs. 71 percent (P less than or equal to 0.002 for all comparisons).

Once-daily bedtime dosing of ZEGERID 40 mg also achieved better nocturnal gastric acid control than twice-daily dosing of Protonix 40 mg: median gastric pH was 4.7 vs. 1.7 (P less than 0.001); the time with gastric pH greater than 4 was 55 percent vs. 34 percent (P less than 0.001); and patients with NAB totaled 53 percent vs. 75 percent (P = 0.035). In addition, ZEGERID 40 mg dosed once-daily achieved similar 24-hour pH control as Protonix 40 mg dosed twice-daily.

Important Safety Information

ZEGERID Powder for Oral Suspension 40 mg is indicated for reduction of risk of upper GI bleeding in critically ill patients and short-term treatment (four to eight weeks) of active benign gastric ulcers. ZEGERID Powder for Oral Suspension 20 mg is indicated for short-term treatment of active duodenal ulcers, for heartburn and other symptoms associated with GERD, for short-term treatment (four to eight weeks) of erosive esophagitis diagnosed by endoscopy, and for maintenance of healing of erosive esophagitis (controlled studies do not extend beyond 12 months). ZEGERID is contraindicated in patients with known hypersensitivity to any components of the formulation.

The most frequently reported adverse events with ZEGERID are headache, diarrhea and abdominal pain. Symptomatic response to therapy does not preclude the presence of gastric malignancy. Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long term with omeprazole. In critically ill patients treated with ZEGERID, adverse events generally reflected the serious, underlying medical condition of the patients, and were similar for patients treated with ZEGERID and with the comparator (acid-controlling) drug.

ZEGERID contains 460 mg sodium per dose in the form of sodium bicarbonate (1680 mg/20 mEq), which should be considered for patients on a sodium-restricted diet. Sodium bicarbonate is contraindicated in patients with metabolic alkalosis and hypocalcemia.

NDA Filed for Omeprazole Chewable Tablets

Fri, 27 May 2005 17:45:38 PST

( from http://www.rxpgnews.com ) Santarus, Inc. (NASDAQ:SNTS), a specialty pharmaceutical company focused on therapies for gastrointestinal diseases and disorders, today announced that it has submitted a New Drug Application (NDA) for ZEGERID(R) (omeprazole) Chewable Tablets 40 mg and 20 mg to the U.S. Food and Drug Administration (FDA).

The Company is seeking marketing approval of ZEGERID Chewable Tablets as the first immediate-release proton pump inhibitor (PPI) in a chewable tablet formulation for the treatment of heartburn and other symptoms associated with gastroesophageal reflux disease (GERD), erosive esophagitis, duodenal ulcers and gastric ulcers. The company is currently marketing ZEGERID Powder for Oral Suspension 40 mg and 20 mg, which is also an immediate-release PPI product. ZEGERID Powder for Oral Suspension is rapidly absorbed (reaching peak plasma levels in approximately 30 minutes) and has strong 24-hour acid control with once-a-day dosing.

"Within the past month, we have submitted NDAs for ZEGERID Capsules and Chewable Tablets, moving us closer to expanding our immediate-release ZEGERID product family. We believe these formulations may provide attractive and convenient immediate-release alternatives for patients suffering from GERD and other upper GI diseases and disorders," said Gerald T. Proehl, president and chief executive officer of Santarus. "Filing the NDA for immediate-release ZEGERID Chewable Tablets is also significant as no other PPI is currently sold as a chewable tablet."

Under the Prescription Drug User Fee Act (PDUFA) guidelines, assuming the FDA accepts the NDA submissions for ZEGERID Capsules and Chewable Tablets, the company expects the FDA to take action on the capsule NDA in late February 2006 and on the chewable tablet NDA in late March 2006, approximately ten months after each NDA submission.

The NDA for ZEGERID Chewable Tablets includes data from two pivotal pharmacokinetic/pharmacodynamic (PK/PD) clinical trials, one for the 40 mg tablet and one for the 20 mg tablet, which were completed in February 2005. The trials were open-label, randomized, crossover trials, each conducted at a single site. Each trial evaluated the PK/PD profiles of ZEGERID Chewable Tablets and delayed-release omeprazole capsules in an equivalent dosage strength in 36 healthy subjects. The primary objective of the trials was to evaluate whether the immediate-release ZEGERID Chewable Tablets were pharmacokinetically equivalent to delayed-release omeprazole capsules with respect to total systemic bioavailability (AUC) on trial day 7. The trials also assessed whether ZEGERID Chewable Tablets and the delayed-release omeprazole capsules had similar ability to suppress gastric acidity over 24 hours. The trial results demonstrated that ZEGERID Chewable Tablets and the delayed-release omeprazole capsules were statistically equivalent with respect to AUC and percent decrease from baseline in gastric acidity on trial day 7. The safety profile of ZEGERID Chewable Tablets was similar to that of delayed-release omeprazole capsules.

As expected for an immediate-release product, the maximum plasma concentration (Cmax) was greater and the time to maximum plasma concentration (Tmax) was shorter on trial day 7 for ZEGERID Chewable Tablets than for the delayed-release omeprazole capsules. These results are similar to those obtained in the pivotal PK/PD trials that were conducted for ZEGERID Powder for Oral Suspension 40 mg and 20 mg. ZEGERID Powder for Oral Suspension 20 mg received FDA approval in June 2004, and the 40 mg formulation was approved in December 2004.

The NDA for ZEGERID Chewable Tablets was submitted under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act which allows an alternative path for FDA approval of new or improved formulations of previously approved products. If the NDA is accepted for filing by the FDA, Santarus will provide notice to the NDA holder for Prilosec(R) delayed-release omeprazole capsules and related patent holders that ZEGERID Chewable Tablets 40 mg and 20 mg do not infringe the patents listed in the Orange Book for Prilosec or that those patents are invalid.

Esomeprazole can reduce upper GI symptoms in patients using NSAIDS

Fri, 13 May 2005 17:03:38 PST

( from http://www.rxpgnews.com ) Results from two clinical trials, published in the American Journal of Gastroenterology, demonstrate that NEXIUM® (esomeprazole magnesium) can reduce upper gastrointestinal (GI) symptoms such as moderate to severe pain, burning and discomfort in the upper abdomen associated with continuous, daily use of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors.

In the trials, NEXIUM 20 mg and 40 mg significantly improved upper GI symptoms in patients taking NSAIDs, including selective COX-2 inhibitors, versus placebo.

People who use NSAIDs regularly are at a high risk for upper GI disturbances including dyspepsia, abdominal pain, and heartburn. Although reducing the NSAID dosage or discontinuing therapy might ease GI symptoms, these alterations often are not an option for many patients because of the chronic nature of their underlying condition, said James M. Scheiman, M.D., Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. These two trials demonstrate that NEXIUM was effective in reducing upper GI symptoms of patients on chronic NSAID therapy.

NEXIUM improved symptoms in as early as the second day of treatment and provided significantly faster symptom relief, compared with placebo. In one trial, 7 consecutive days of symptom relief occurred within an average of 11 and 10 days for patients treated with NEXIUM 20 mg and 40 mg, respectively, versus 17 days for placebo. In the other trial, 7 consecutive days of symptom relief occurred within an average of 10 and 11 days for patients treated with NEXIUM 20 mg and 40 mg, respectively, versus 21 days for placebo.

In addition, over the four week treatment period, the proportion of symptom-free days was significantly higher for patients treated with NEXIUM versus placebo in both trials (31 percent and 29 percent, vs. 21 percent, and 29 percent and 27 percent, vs. 14 percent in the two trials). More patients treated with NEXIUM (20 mg or 40 mg) also reported improvements on an overall treatment assessment after four weeks of treatment, versus placebo (70.6 percent and 56.8 percent for NEXIUM 20 mg, and 61.1 percent and 54.7 percent for NEXIUM 40 mg, compared with 47.7 percent and 40.9 percent for placebo in these trials).

About the Trials The clinical research trials were two identical, randomized, double-blind, placebo-controlled trials involving a total of 595 and 554 patients, respectively, who were continuous NSAID users and who did not have gastric ulcers, erosive esophagitis or H. pylori infection. Approximately one-third of the patients in both trials (30 percent, 38 percent) were taking only selective COX-2 inhibitors. In the trials, patients received NEXIUM 20 mg or 40 mg or placebo.

In both trials, the safety profile of NEXIUM 20 mg and 40 mg among continuous NSAID users was similar to placebo.