Affects of Once-daily Oral Administration of TZP-102 on the Treatment of Symptoms Associated With Diabetic Gastroparesis

Study Overview
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Brief Summary
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The purpose of this study is to test the safety and effectiveness of two dosage levels (10mg and 20mg) of TZP-102 compared to placebo (capsule that looks like the study drug but contains no active drug), administered once-daily for 12 weeks, in diabetic subjects with symptoms associated with gastroparesis.

Detailed Description
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Considered subjects will be screened to determine eligibility for entry into the study. The Screening Visit must take place at least 14 days, but not more than 21 days, before the planned date of study entry (randomization and administration of the first dose of study drug on Study Day 1). The baseline evaluation of gastric emptying must be scheduled at least 7 days (in the U.S.) and 10 days (in Europe) before the Day 1 Visit. Subjects will answer questions relating to their gastroparesis symptoms in an electronic diary (like a palm pilot) beginning on the first day of the screening period. Eligible subjects will be randomized to receive placebo or one of two dosages of TZP-102 (10mg or 20mg) once daily for 12 weeks. After randomization and administration of the first dose of study drug on Study Day 1 (the Study Entry Visit), subsequent visits to the clinic will be scheduled every two weeks during the 12-week Treatment period and 4-week Follow-Up Period. All visits will be conducted on an outpatient basis. Visits for a given subject throughout the study should be scheduled to start at approximately the same time, in the morning. Subjects will be instructed to take their daily dose of study drug each morning (when not attending a study visit), at least 30 minutes before breakfast. Subjects will be instructed to not take study drug on the morning of each treatment period visit and to bring study drug supplies with them to the clinic; study drug will be administered in the clinic after all scheduled assessments/procedures (after all pre-dose assessments at each of the Day 1 and Week 12 Visits) are completed.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Evaluation of the Efficacy and Safety of Once-Daily Administrations of TZP-102 for the Treatment of Symptoms Associated With Diabetic Gastroparesis

Conditions
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Gastroparesis, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo
* Drug: 10mg TZP-102
* Drug: 20mg TZP-102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 80 years of age, inclusive Type 1 or type 2 diabetes mellitus History of symptoms of gastroparesis for at least 3 months leading up to the Screening Visit Gastric half-emptying time >82 minutes, demonstrated by the Gastric Emptying Breath Test performed at the Screening Visit OR documented delayed gastric emptying within the previous 24 months Mild to moderate severity of gastroparesis symptoms during the screening period Body Mass Index (BMI) < 45.0 at the Screening Visit Glycosylated hemoglobin (HbA1c) level < 11.0% at the Screening Visit Upper gastrointestinal obstruction ruled out by endoscopy or barium scan Concomitant medications must be stable for at least 2 weeks leading up to the Baseline Visit and must be maintained during the study. Females of child-bearing potential must have a negative serum pregnancy test and use (and agree to continue to use throughout the study) an acceptable form of contraception. Exclusion Criteria: Persistent daily vomiting Gastrectomy, bariatric surgery, fundoplication or vagotomy/pyloroplasty Has had or plans to have endoscopic pyloric injections of botulinum toxin within 6 months prior to the Screening Visit or during the study. NG, PEG or PEJ feeding tube within 2 weeks prior to the Screening Visit Required in-patient hospitalization for treatment of gastroparesis within 2 weeks prior to the Screening Visit Required parenteral nutrition for treatment of gastroparesis within 2 months prior to the Screening Visit Active gastric pacemaker within 3 months prior to the Screening Visit Participated in an investigational study within 30 days prior to the Screening Visit Chronic severe diarrhea Diabetic ketoacidosis that required inpatient hospitalization within 30 days prior to the Screening Visit History of any eating disorder within 2 years prior to the Screening Visit Chronic obstructive pulmonary disease (COPD) or chronic asthma Chronic smoker that is unable or unwilling to abstain from smoking during the two visits that the gastric emptying breath test will be performed History of risk factors for Torsades de Pointes Corrected QT interval calculated using Fredericia's formula >= 500 msec, recorded and confirmed on any of the three ECG assessments performed during the screening period Bradycardia or hypotension assessed as clinically-significant by the investigator Requires treatment with concomitant medication that is a substrate of Cytochrome P450 isoenzyme 3A4 and known to have a clinically recognized risk for Torsades de Pointes History of acute myocardial infarction, unstable angina or a transient (cerebral) ischemic attack within 12 months prior to the Screening Visit History of severe depression, psychiatric disorder or cognitive impairment History of alcohol or drug abuse or dependency within 2 years prior to the Screening Visit Taking opiates for abdominal pain Known history of Hepatitis B or C or HIV infection Requires dialysis or elevated creatinine at the Screening Visit Abnormal liver function tests at the Screening Visit Uncontrolled hypo- or hyperthyroidism Adrenal insufficiency Active malignancy other than basal cell or squamous cell carcinoma of the skin Pregnant or breast-feeding Allergies to components of the breath test meal or severe lactose intolerance Any other medical condition or social circumstance that, in the investigator's opinion, makes it inappropriate for the patient to participate in this clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Drug: placebo | Drug: Placebo<br>* Two #2 oval shaped,opaque-white, hard gelatin shell capsules containing inactive ingredients taken orally once daily for 12 weeks.<br>|
| Experimental: 2<br>10mg TZP-102 | Drug: 10mg TZP-102<br>* One 10mg #2 oval shaped, opaque-white, hard gelatin shell capsule containing active ingredients and one placebo capsule each taken orally once daily for 12 Weeks<br>|
| Experimental: 3<br>20mg TZP-102 | Drug: 20mg TZP-102<br>* Two 10mg #2 oval shaped, opaque-white, hard gelatin shell capsules containing active ingredients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in symptoms associated with diabetic gastroparesis |  | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline on health-related quality of life |  | 12 Weeks | 
| Adverse Events (AEs) |  | 12 Weeks | 
| Cardiovascular Parameters (blood pressure, heart rate, 12-Lead ECG) |  | 12 Weeks | 
| Clinical Chemistry and Hematology Parameters |  | 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetic gastroparesis, delayed gastric emptying, gastroparesis, diabetes mellitus, Type 1, diabetes mellitus, Type 2