Tranzyme Inc

NC, United States

Tranzyme Inc

NC, United States
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Ejskjaer N.,Aarhus University Hospital | Wo J.M.,Indiana University | Esfandyari T.,University of Kansas Medical Center | Mazen Jamal M.,Long Beach Medical Center | And 8 more authors.
Neurogastroenterology and Motility | Year: 2013

Background Gastroparesis causes significant morbidity and treatment options are limited. TZP-102 a novel, macrocyclic, selective, oral ghrelin receptor agonist, was evaluated in a randomized, double-blind, placebo-controlled trial in patients with diabetic gastroparesis. Methods A total of 92 outpatients were randomized to once-daily administrations of 10-mg (n=22), 20-mg (n=21), 40-mg (n=23) TZP-102 or placebo (n=26). The primary endpoint was the change from baseline in gastric half-emptying time (T1/2) utilizing 13C-breath test methodology and secondary endpoints included symptom improvement using patient-reported gastroparesis symptom scores (PAGI-SYM questionnaire) and patient and physician overall treatment evaluations (OTE). Key Results Gastric T1/2 changes were not statistically significant between TZP-102 and placebo after 28days of treatment at any dose. Clinical improvements (-1.0 to -1.4 point mean decrease in symptom severity) occurred in the Gastroparesis Cardinal Symptom Index (GCSI) component of the PAGI-SYM, which was significant vs placebo for all TZP-102 doses combined. Improvements became evident after 1week of treatment. Significantly, more patients given TZP-102 (any dose) had a 50% reduction in baseline GCSI score (28.8%vs 7.7% placebo). Safety profiles were similar across groups. All TZP-102 doses were well-tolerated with no adverse cardiac, weight, or glucose control outcomes. Conclusions & Inferences TZP-102 for 28days, at doses of 10-40mg once daily, was well-tolerated and resulted in a reduction in symptoms of gastroparesis. The lack of correlation between symptom improvement and gastric emptying change is consistent with previous studies in diabetic gastroparesis, and emphasizes the value of patient-defined outcomes in determining therapeutic benefit. © 2012 Blackwell Publishing Ltd.


Mccallum R.W.,Texas Tech University Health Sciences Center | Lembo A.,Beth Israel Deaconess Medical Center | Esfandyari T.,University of Kansas Medical Center | Bhandari B.R.,Delta Research Partners | And 6 more authors.
Neurogastroenterology and Motility | Year: 2013

Background: TZP-102, a potent, oral, ghrelin receptor agonist, improved diabetic gastroparesis symptoms in Phase 2a. Methods: Patients with type 1 or 2 diabetes, delayed gastric half-emptying (T1/2), and ≥3 months gastroparesis symptoms randomized 1 : 1 : 1 to double-blind placebo, 10-mg, or 20-mg TZP-102 once daily for 12 weeks (Study TZP-102-CL-G003). Study TZP-102-CL-G004 patients randomized 1 : 1 to 10-mg TZP-102:placebo three-times-daily. Primary endpoint was change-from-baseline through Weeks 11-12 in Daily Diary of Gastroparesis Symptoms Questionnaire (GSDD) via electronic Patient Recorded Outcome device: worst severity of nausea, early satiety, bloating, and upper abdominal pain in 24 h (0 = none-to-5 = very severe). GSDD Composite Score for eligibility was ≥2.5 (Day-14-to-baseline). Patient Overall Treatment Evaluation (OTE) provided an anchor-based minimal clinically important difference (MCID) for GSDD Composite Score. Key Results: Study TZP-102-CL-G003 enrolled 201 outpatients: females 72%; Caucasians 87%; type 2 diabetes 61%; insulin-dependent 65%; age mean ± SD 53 ± 11.3 years; HbA1c 7.8 ± 1.5%; GCSI 3.4 ± 0.7; GSDD Composite 3.6 ± 0.6; gastric T1/2 131 ± 32 min; n = 69 (10-mg), n = 66 (20-mg), n = 66 (placebo). Primary endpoint (GSDD): significant improvement in all arms, although not for TZP-102 vs placebo: mean change-from-baseline -1.7, -1.4, -1.5 (10-mg, 20-mg, placebo); Gastroparesis Cardinal Symptom Index -1.8, -1.6, -1.5, respectively. The OTE (all patients) at Week-12 was: Patient 3.7 ± 3.2 and Physician 3.6 ± 3.0 with median score for both of 5.0 = important on scale of improvement; individual MCID was 1.61 and 0.94 for group analyses, greater than expected. Study TZP-102-CL-G004 with similar demographic/disease characteristics was prematurely terminated for efficacy futility (n = 64 with Week-4 assessments). Conclusions & Inferences: Efficacy of TZP-102 was not demonstrated compared with placebo in diabetic gastroparesis; however, there was substantial symptom improvement in all arms inclusive of placebo. © 2013 John Wiley & Sons Ltd.


Bochicchio G.,University of Maryland, Baltimore | Charlton P.,Tranzyme Inc | Pezzullo J.C.,Georgetown University | Kosutic G.,Tranzyme Inc | Senagore A.,University of Southern California
World Journal of Surgery | Year: 2012

Background Delayed recovery of gastrointestinal (GI) motility is a common complication following surgery. TZP-101/ulimorelin is a macrocyclic peptidomimetic ghrelin receptor agonist with GI promotility effects that significantly accelerates time to recovery of GI motility compared to placebo following partial colectomy. It is also well tolerated. The objectives of this analysis were to identify predictors of GI motility recovery in patients undergoing partial colectomy and to evaluate whether these factors affect ulimorelin acceleration of GI recovery. Methods Covariate analysis assessed the effect of eight variables-age, sex, body mass index, type of surgery (right colectomy, left colectomy, other), duration of surgery, blood loss, total opioid consumption, country-on recovery of GI motility in 236 patients randomized to ulimorelin (n = 168) or placebo (n = 68). The primary endpoint was the recovery of GI function (time from the end of surgery to first bowel movement). Stepwise regression identified a parsimonious model of the smallest subset of variables best predicting GI recovery. Results Recovery was shorter for segmental/subtotal colectomies vs. right colectomies (P = 0.016) and longer with increased total opioid use (P = 0.037). The remaining variables had no statistically significant effect on GI recovery. Effects of ulimorelin 480 lg/kg (the most effective dose) on time to GI tract recovery remained statistically and clinically significant (hazard ratio = 1.81, P = 0.014) when adjusted for surgery type and/or total opioid use. Conclusions Two factors, type of surgery and total opioid use, independently modified times to recovery of GI motility following partial large bowel resection surgery. Acceleration of recovery of GI motility by ulimorelin was independent of these factors. © Société Internationale de Chirurgie 2011.


Shaw M.,Norgine Ltd | Pediconi C.,Norgine Ltd | McVey D.,Norgine Ltd | Mondou E.,Tranzyme Inc | And 3 more authors.
Diseases of the Colon and Rectum | Year: 2013

Background: Gastrointestinal recovery is a critical milestone after bowel resection with postoperative ileus resulting in increased risk of complications and prolonged hospitalization. Objective: The aim of this study is to evaluate the efficacy and safety of ulimorelin, a ghrelin receptor agonist given postoperatively in 2 identically designed phase 3 studies (ClinicalTrials.gov NCT01285570 and NCT01296620). Design: This investigation is designed as a multicenter, double-blind, randomized, parallel-group study. Settings: This study involves hospital inpatients. Patients: Adult patients undergoing partial bowel resection were included. Intervention: Thirty-minute intravenous infusions (160 μg/kg, 480 μg/kg ulimorelin, or placebo) once daily were started within 60 minutes after the end of surgery and ended at the first of the following: primary efficacy end point fulfilled (defined below), hospital discharge, or 7 days treatment. Main Outcome Measures: The primary efficacy end point was the time from the end of surgery to the composite end point of the later of first bowel movement and tolerance of solid food. Safety was assessed with the use of standard assessments including adverse events and laboratory tests. Results: Ulimorelin Study of Efficacy and Safety 007, n = 332 patients; Ulimorelin Study of Efficacy and Safety 008, n = 330 patients: in both studies, the primary efficacy end point and the secondary efficacy outcomes, which included postsurgical time to first bowel movement, tolerance of solid food, and discharge eligibility, did not differ significantly among patients treated with either dose of ulimorelin versus placebo. Rates of serious adverse events were comparable across all treatment groups. There was no statistically significant difference from placebo in regard to events of interest, namely nausea, vomiting, ileus as an adverse event, nasogastric tube reinsertion, anastomotic complications, and infections. Limitations: A possible limitation is the variance inherent in surgery and comorbidities. Conclusions: Although the efficacy of ulimorelin in reducing the duration of postoperative ileus was not demonstrated in these studies, intravenous ulimorelin at doses of 160 μg/kg and 480 μg/kg was generally well tolerated in postcolectomy patients. Similar to other promotility agents, ulimorelin may find an application in other indications better suited to its attributes. Copyright © The ASCRS 2013.


Wo J.M.,University of Louisville | Ejskjaer N.,Aarhus University Hospital | Hellstrom P.M.,Uppsala University | Malik R.A.,University of Manchester | And 5 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2011

Aliment Pharmacol Ther 2011; 33: 679-688 Summary Background Limited therapeutic options exist for severe gastroparesis, where severe nausea and vomiting can lead to weight loss, dehydration and malnutrition due to inadequate caloric and fluid intake. TZP-101 (ulimorelin) is a ghrelin receptor agonist that accelerates gastric emptying and improves upper gastrointestinal symptoms in diabetic patients with gastroparesis. Aim To assess effects of TZP-101 in diabetic gastroparesis patients with severe nausea/vomiting and baseline severity scores of ≥3.5 (range: 0-5) on the Gastroparesis Cardinal Symptom Index (GCSI) Nausea/Vomiting subscale. Methods Patients were hospitalised and received four single daily 30-min infusions of one of six TZP-101 doses (range 20-600 μg/kg) or placebo. Efficacy was assessed by symptom improvement. Results At baseline, 23 patients had a mean severity score for GCSI Nausea/Vomiting of 4.45 ± 0.44. Statistically significant improvements over placebo occurred in the 80 μg/kg group for end of treatment changes from baseline in GCSI Nausea/Vomiting subscale (reduction in score of -3.82 ± 0.76, P = 0.011) and the GCSI Total score (-3.14 ± 0.78, P = 0.016) and were maintained at the 30-day follow-up assessment (-2.02 ± 1.63, P = 0.073 and -1.99 ± 1.33, P = 0.032 respectively). The proportion of days with vomiting was reduced significantly (P = 0.05) in the 80 μg/kg group (mean of 1.2 days of vomiting for four treatment days) compared with placebo (mean of 3.2 days of vomiting across 4 treatment days). Conclusions TZP-101 substantially reduced the frequency and severity of nausea and vomiting as well as overall gastroparesis symptoms. The results are consistent with gastrointestinal motility effects of TZP-101, supporting further investigation of TZP-101 in the management of severe gastroparesis. © 2011 Blackwell Publishing Ltd.


Trademark
Tranzyme Inc. | Date: 2012-02-06

Pharmaceutical preparations for human use.


Trademark
Tranzyme Inc. | Date: 2012-02-06

Pharmaceutical preparations for human use.


Trademark
Tranzyme Inc. | Date: 2012-02-06

Pharmaceutical preparations for human use.


Trademark
Tranzyme Inc. | Date: 2012-02-06

Pharmaceutical preparations for human use.


Trademark
Tranzyme Inc. | Date: 2012-02-06

Pharmaceutical preparations for human use.

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