The medical condition to be investigated is symptomatic gastroparesis due to diabetes mellitus MedDRA version: 14.1 Level: LLT Classification code 10018043 Term: Gastroparesis System Organ Class: 100000004856
Conditions
Interventions
Product Name: TZP-102
Product Code: TZP-102
Pharmaceutical Form: Capsule
Current Sponsor code: TZP-102
Other descriptive name: Sesquiphosphate hydrate
Concentration unit: mg milligram(s)
Concentration
Sponsors
Tranzyme, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient must be 18 to 80 years of age, inclusive. 2. Patient has type 1 or type 2 diabetes mellitus. 3. Patient has a history of symptoms of gastroparesis (nausea, early satiety, bloating, upper abdominal pain, retching and/or vomiting) for at least 3 months leading up to the Screening Visit. 4. Patient has delayed gastric emptying, defined as a gastric half-emptying time (T½) > 82 minutes, demonstrated by the [13C]-Spirulina platensis Gastric Emptying Breath Test (GEBT) performed during the Screening Period or has a documented delayed gastric emptying within 24 months by either scintigraphy or GEBT 5. Patient has an average Daily Diary of Gastroparesis Symptoms Questionnaire (GSDD) Composite Symptom Severity Score bigger and/or equal to 2.5 during the final 14 days of the Screening Period leading up to the Day 1 Visit (and the possible initiation of randomized study treatment). [The GSDD Composite Symptom Severity Score (GSDD Composite Score) is defined as the mean of the four individual symptom severity scores for nausea, early satiety, bloating and upper abdominal pain, each graded on a 6-point scale (0 = none; 1 = very mild; 2 = mild; 3 = moderate; 4 = severe; and 5 = very severe).] 6. Patient has a Body Mass Index (BMI) 30 days prior to the Screening Visit, barrier (e.g., condom, diaphragm with spermicide), intra-uterine device (IUD) or vasectomized partner (6 months minimum). If required by the Regulatory/Competent Authorities in a specific country or by any given study site’s Institutional Review Board (IRB) or Independent Ethics Committee (IEC), male patients must also agree to practice throughout the study an approved method of birth control. [Note: To be considered NOT of childbearing potential, female patients must be postmenopausal (with amenorrhea for at least 2 years prior to study entry) or surgically sterile (with physician or insurance documentation of bilateral tubal ligation at least 6 months prior to study en
Exclusion criteria
Exclusion criteria: 1. Patient has persistent daily vomiting that would preclude daily oral intake. 2. Patient had a gastrectomy, obesity surgery (gastric bypass, vertical banding gastroplasty, lap band), fundoplication, or vagotomy/pyloroplasty. 3. Patient had endoscopic pyloric injections of botulinum toxin within 6 months prior to the Screening Visit. (This procedure is also prohibited during the full duration of the study.) 4. Patient has a nasogastric (NG), percutaneous endoscopic gastrostomy (PEG) or percutaneous endoscopic jejunostomy (PEJ) feeding tube. If the patient recently had a feeding tube in place, it must have been removed at least 2 weeks prior to the Screening Visit. 5. Patient required inpatient hospitalization for treatment of his/her gastroparesis within 2 weeks prior to the Screening Visit. [Note: “Inpatient” means that the patient has been formally admitted to the hospital. This may or may not be overnight. It does not include presentation to an outpatient care facility or emergency room.] 6. Patient required parenteral nutrition for treatment of his/her gastroparesis within 2 months prior to the Screening Visit, or is expected to require parenteral nutrition within 1 month after study entry. 7. Patient has (or had within the 3 months leading up to the Screening Visit) an active gastric pacemaker (electrical neurostimulator). [Note: if an inactive gastric pacemaker is still in place, it may not be activated during the course of the study.] 8. Patient participated in an investigational study within 30 days prior to the Screening Visit (or, if longer, within five half-lives of the last dose of any investigational drug). [Note: the use of domperidone (an investigational drug in the U.S.) is not permitted within 14 days prior to the Screening Visit, and is not permitted during the study.] 9. Patient has chronic severe diarrhea. [Note: Patients with a history of intermittent diarrhea, or chronic mild diarrhea, may still be considered for study participation.] 10. Patient had diabetic ketoacidosis that required inpatient hospitalization within 30 days prior to the Screening Visit. 11. Patient has a history of any eating disorder (anorexia nervosa, binge eating, bulimia) within 2 years prior to the Screening Visit. 12. Patient has significant, symptomatic chronic obstructive pulmonary disease (COPD) or chronic asthma that would interfere with performing the two gastric emptying breath tests during the study. 13. Patient is a heavy smoker and unable or unwilling to abstain from smoking during each of the two 4- to 5-hour study visits during which the gastric emptying breath tests will be performed. 14. Patient has a history of risk factors for Torsades de Pointes (heart failure, chronic hypokalemia, a personal diagnosis or family history of Long QT Syndrome). 15. Patient has a corrected QT interval calculated using Fredericia’s formula (QTcF) = 500 msec recorded on any of the three 12-lead electrocardiography (ECG) assessments performed during the Screening Period. 16. Patient has clinically-significant bradycardia or hypotension, as judged by the Investigator. 17. Patient requires treatment with any concomitant medication that is both a substrate of Cytochrome P450 isoenzyme 3A4 and known to have a clinically recognized risk for Torsades de Pointes. 18. Patient has a history of an acute myocardial infarction, unstable angina, a cerebral vascular accident or any transient (cerebral) ischemic attack (TIA) wit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the effect of TZP-102 administered three times a day for 12 weeks on symptoms associated with diabetic gastroparesis—specifically, nausea, early satiety, bloating, upper abdominal pain, vomiting and retching;Secondary Objective: to evaluate the safety of TZP-102 administered three times a day for 12 weeks • to assess the effect of TZP-102 on health-related quality of life • to evaluate the pharmacodynamic effects of TZP-102 on serum growth hormone and serum IGF-1 concentrations • to attempt to characterize in a subset of patients the plasma pharmacokinetic profile of TZP 102 administered three times a day • to determine the dosage (schedule of administration) of TZP-102 to evaluate in Phase 3 of clinical development ;Primary end point(s): -Change from baseline in the GSDD symptom scores using methods to be specified in the statistical analysis plan;Timepoint(s) of evaluation of this end point: - For change from baseline in GSDD symptom scores, during the final 14 days of the Screening Period that precede the Day 1 Visit. Primary analysis is prospectively planned based on projected database lock following completion of the 12-week treatment period and assessments by the last randomized patient since on-treatment measures of potential activity/therapeutic effect are of primary clinical interest. -The Patient and Physician OTE scores at each of the Week 4, 8 and 12 Visits, -Change from baseline in the Patient assessment of Overall Severity of Gastroparesis Symptoms (1-week recall) Score at each of the Week 2 and Week 12 Visits, -Change from baseline in health-related Quality of Life, based on the scoring of the PAGI-QOL Questionnaire, at the end of the 12-week Treatment Period, | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Please refer to protocol section 11.5;Secondary end point(s): -The proportion of patients who achieve a pre-specified decrease from baseline in the GSDD symptom scores during the 12-week Treatment Period will be analyzed using methods to be specified in the statistical analysis plan. - Change from baseline in the number of times the patient vomited during the 12-week Treatment Period will be analyzed using methods to be specified in the statistical analysis plan. - Change from baseline in the number of times the patient retched during the 12-week Treatment Period will be analyzed using methods to be specified in the statistical analysis plan. - Frequency (the number of patients) with one or more inpatient hospitalization(s) during the study (after randomization through the final, Week 16 Follow-Up Visit), will be analyzed using methods to be specified in the statistical analysis plan [“Inpatient” means that the patient has been formally admitted to a hospital. This may or may not require an overnight stay. It does not include presentation to an outpatient care facility or emergency room.] | — |
Countries
Poland, United States
Contacts
Public ContactMarcin Puchow
PharmaTrials-Polska Sp. z o.o.
Outcome results
None listed