PMID- 23848826
OWN - NLM
STAT- MEDLINE
DCOM- 20140813
LR  - 20131004
IS  - 1365-2982 (Electronic)
IS  - 1350-1925 (Linking)
VI  - 25
IP  - 11
DP  - 2013 Nov
TI  - Phase 2b, randomized, double-blind 12-week studies of TZP-102, a ghrelin receptor 
      agonist for diabetic gastroparesis.
PG  - e705-17
LID - 10.1111/nmo.12184 [doi]
AB  - 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 (T(1/2)), 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 
      (ClinicalTrials.gov NCT01452815/NCT01664637).
CI  - (c) 2013 John Wiley & Sons Ltd.
FAU - McCallum, R W
AU  - McCallum RW
AD  - Department of Internal Medicine, Texas Tech University Health Sciences Center, El 
      Paso, TX, USA.
FAU - Lembo, A
AU  - Lembo A
FAU - Esfandyari, T
AU  - Esfandyari T
FAU - Bhandari, B R
AU  - Bhandari BR
FAU - Ejskjaer, N
AU  - Ejskjaer N
FAU - Cosentino, C
AU  - Cosentino C
FAU - Helton, N
AU  - Helton N
FAU - Mondou, E
AU  - Mondou E
FAU - Quinn, J
AU  - Quinn J
FAU - Rousseau, F
AU  - Rousseau F
CN  - TZP-102 Phase 2b Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT01452815
SI  - ClinicalTrials.gov/NCT01664637
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130715
PL  - England
TA  - Neurogastroenterol Motil
JT  - Neurogastroenterology and motility
JID - 9432572
RN  - 0 (Macrocyclic Compounds)
RN  - 0 (Receptors, Ghrelin)
SB  - IM
CIN - Neurogastroenterol Motil. 2013 Nov;25(11):859-63. PMID: 24001134
MH  - Diabetes Mellitus, Type 1/*complications
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Double-Blind Method
MH  - Female
MH  - Gastric Emptying/*drug effects
MH  - Gastroparesis/*drug therapy/etiology
MH  - Humans
MH  - Macrocyclic Compounds/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Receptors, Ghrelin/*agonists
OTO - NOTNLM
OT  - diabetes type 1
OT  - diabetes type 2
OT  - diabetic gastroparesis
OT  - oral ghrelin receptor agonist
FIR - Arts, J
IR  - Arts J
FIR - Tarnow, L
IR  - Tarnow L
FIR - Yderstraede, K
IR  - Yderstraede K
FIR - Lahtela, J T
IR  - Lahtela JT
FIR - Punkkinen, J M
IR  - Punkkinen JM
FIR - Dimcevski, G
IR  - Dimcevski G
FIR - Bandurska-Stankiewicz, E
IR  - Bandurska-Stankiewicz E
FIR - Jakubowska, I L
IR  - Jakubowska IL
FIR - Loba, J
IR  - Loba J
FIR - Majcher-Witczak, G
IR  - Majcher-Witczak G
FIR - Muszynski, J
IR  - Muszynski J
FIR - Trznadel-Morawska, I
IR  - Trznadel-Morawska I
FIR - Zarzycki, W
IR  - Zarzycki W
FIR - Hellstrom, P M
IR  - Hellstrom PM
FIR - Lindberg, G V V
IR  - Lindberg GV
FIR - Ayub, K
IR  - Ayub K
FIR - Barish, C F
IR  - Barish CF
FIR - Beltzer, L
IR  - Beltzer L
FIR - Bennetts, R W
IR  - Bennetts RW
FIR - Breton, C F
IR  - Breton CF
FIR - Clift, S A
IR  - Clift SA
FIR - Garner, B M
IR  - Garner BM
FIR - Goetsch, C A
IR  - Goetsch CA
FIR - Gonzalez, J O
IR  - Gonzalez JO
FIR - Gopal, V D
IR  - Gopal VD
FIR - Gordon, G L
IR  - Gordon GL
FIR - Graf, R J
IR  - Graf RJ
FIR - Gross, C G
IR  - Gross CG
FIR - Hazan, S
IR  - Hazan S
FIR - Hellstern, P A
IR  - Hellstern PA
FIR - Holmes, R J
IR  - Holmes RJ
FIR - Jagarlamudi, K K
IR  - Jagarlamudi KK
FIR - Jamal, M M
IR  - Jamal MM
FIR - Kodali, V P
IR  - Kodali VP
FIR - Miner, P B
IR  - Miner PB
FIR - Nowak, T V
IR  - Nowak TV
FIR - Nguyen, L A B
IR  - Nguyen LA
FIR - Souder, B T
IR  - Souder BT
EDAT- 2013/07/16 06:00
MHDA- 2014/08/15 06:00
CRDT- 2013/07/16 06:00
PHST- 2013/03/20 00:00 [received]
PHST- 2013/06/17 00:00 [accepted]
PHST- 2013/07/16 06:00 [entrez]
PHST- 2013/07/16 06:00 [pubmed]
PHST- 2014/08/15 06:00 [medline]
AID - 10.1111/nmo.12184 [doi]
PST - ppublish
SO  - Neurogastroenterol Motil. 2013 Nov;25(11):e705-17. doi: 10.1111/nmo.12184. Epub 
      2013 Jul 15.