Business Wire - Questcor Reports Results of a Phase II Study of Emitasol in Diabetic Gastroparesis
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HAYWARD, Calif.–(BUSINESS WIRE)–Oct. 19, 2000
Questcor Pharmaceuticals Inc. (AMEX:QSC) announced today the results of the Phase II study of Emitasol(R) (Metoclopramide, Nasal Spray) in the treatment of diabetic gastroparesis, a serious complication of diabetes that substantially reduces quality of life. The study found encouraging results in terms of safety and a preliminary evaluation of efficacy.
In this open-label, multicenter Phase II study, 89 subjects, diagnosed with diabetes and symptoms of gastroparesis, were randomized to three treatment groups: 18 subjects received oral metoclopramide at 10 mg q.i.d., 35 received Emitasol(R) (Metoclopramide, Nasal Spray) at 10 mg q.i.d. and 36 received Emitasol(R) at 20 mg q.i.d., for a period of six weeks. Pharmacokinetics, safety and preliminary efficacy analyses were performed.
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In summary, the study showed that both Emitasol(R) (Metoclopramide Nasal Spray) and oral metoclopramide were bioavailable when administered to diabetic gastroparesis patients. This study in disease state subjects differed from previous pharmacokinetic studies which were conducted in normal subjects. The trial also suggested that Emitasol(R) (Metoclopramide Nasal Spray) treatment may enhance the clinical response versus oral metoclopramide. No adverse events reported were categorized as serious.
“We are enthusiastic about the potential of Emitasol(R) in diabetic gastroparesis,” said Charles J. Casamento, chairman and CEO of Questcor. “Up to 50% of over 8 million patients with reported diabetes in the U.S. present symptoms or evidence of gastroparesis. We plan to commence the Phase III study in early 2001. We are also looking forward to extending our investigations to other conditions, such as delayed-onset emesis caused by chemotherapy, where current therapeutic regimens are inadequate. Additionally, we continue to explore new partnership opportunities for the marketing of Emitasol(R) outside the U.S. The intranasal delivery route presents specific advantages in terms of compliance and expected pharmacological response in patients that experience persistent vomiting and nausea.”
Efficacy results were of an exploratory nature due to the design of the study, but were positive overall. The subject’s response to the treatment was assessed at baseline and at weekly intervals by a symptom assessment questionnaire (SAQ). Symptoms in the SAQ included nausea, vomiting, anorexia, feeling bloated, feeling full after a small meal and persistent fullness after eating. The analysis of overall SAQ score reduction for subjects completing the study according to the protocol indicated a significantly enhanced response for both the 10 mg and 20 mg Emitasol(R) groups, when compared to the oral metoclopramide 10 mg group (p = 0.026 and p = 0.008, respectively). In individual symptoms, significant improvements in score were observed in the intranasal 20 mg group when compared to the oral 10 mg group in anorexia (p = 0.019), persistent fullness (p = 0.003) and feeling full after a small meal (p = 0.010). The intranasal 10 mg group showed a significantly increased improvement from the oral 10 mg group in feeling full after a small meal (p = 0.021).
The single-dose pharmacokinetic profile of metoclopramide was determined for all treatment groups both at the beginning and the end of treatment. The bioavailability of metoclopramide following its intranasal administration was 68% to 83% when compared to the oral route as the AUC0-t for the 10 mg oral, 10 mg intranasal and 20 mg intranasal doses was 269.5, 224.0 and 366.1 ng/mL, respectively (treatment day 1). There were no significant differences in terminal half-life and in time to reach maximum concentration (Tmax) among the groups. However, there was a lag-time of approximately 20 minutes in the absorption of metoclopramide for the oral group in comparison to the intranasal groups.
The safety of both routes of metoclopramide administration was evaluated by examination of adverse events, active monitoring of nasopharyngeal symptoms, vital signs and hematological and biochemical tests. Seven of the 89 subjects discontinued treatment prior to study completion. Those dropping out were equally distributed among the three treatment arms of the study. Of the adverse events that occurred during the study, none was categorized as serious and most were reported as mild. There was no statistical difference between the treatment groups in adverse events. Significantly more subjects in the intranasal groups reported nasopharynx-related adverse events, mostly nasal irritation. All but two of the nasopharyngeal adverse events were categorized as mild and none as severe. The incidence of neurological adverse events such as sleepiness, nervousness or dizziness was low. Three subjects (16.6%) reported such events in the 10 mg oral group, none (0%) in the 10 mg intranasal and six subjects (16.6%) in the 20 mg intranasal group. There were no extrapyramidal reactions in any subjects.
