Ascending dose-controlled trial of beloranib, a novel obesity treatment for safety, tolerability, and weight loss in obese women

Obesity

Volumn 21, Issue 9, 2013, Pages 1782-1788

  Hughes, T E ^a   Kim, D D ^a   Marjason, J ^b   Proietto, J ^c,d   Whitehead, J P ^a   Vath, J E ^a  

^a One Cambridge Center   (United States)

^b Q Pharm   (Australia)

^c UNIVERSITY OF MELBOURNE   (Australia)

^d MATER MEDICAL RESEARCH INSTITUTE   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXYBUTYRIC ACID; ADIPONECTIN; BELORANIB; C REACTIVE PROTEIN; FIBROBLAST GROWTH FACTOR 21; LEPTIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; METHIONYL AMINOPEPTIDASE 2; PLACEBO; TRIACYLGLYCEROL;

ABNORMAL LABORATORY RESULT; ADULT; AREA UNDER THE CURVE; ARTICLE; BACKACHE; CARDIOMETABOLIC RISK; CLINICAL ARTICLE; CONTROLLED STUDY; CONTUSION; DIARRHEA; DISTRIBUTION VOLUME; DIZZINESS; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ENZYME INHIBITION; FEMALE; HEADACHE; HUMAN; HUNGER; INFUSION RELATED REACTION; MAXIMUM PLASMA CONCENTRATION; MIGRAINE; MULTICENTER STUDY; MUSCULOSKELETAL PAIN; NAUSEA; NECK PAIN; OBESITY; RANDOMIZED CONTROLLED TRIAL; RISK FACTOR; SKIN DISEASE; THORAX PAIN; TIME TO MAXIMUM PLASMA CONCENTRATION; UPPER RESPIRATORY TRACT INFECTION; VASCULAR ACCESS; WEIGHT CHANGE; WEIGHT REDUCTION; XEROSTOMIA;

3-HYDROXYBUTYRIC ACID; ADIPONECTIN; AMINOPEPTIDASES; ANTI-OBESITY AGENTS; ASPERGILLUS; BIOLOGICAL PRODUCTS; BLOOD GLUCOSE; BLOOD PRESSURE; C-REACTIVE PROTEIN; CHOLESTEROL, LDL; CYCLOHEXANES; DOUBLE-BLIND METHOD; FATTY ACIDS, UNSATURATED; FEMALE; FIBROBLAST GROWTH FACTORS; GLYCOPROTEINS; HUMANS; HUNGER; INFUSIONS, INTRAVENOUS; LEPTIN; LIPIDS; MIDDLE AGED; OBESITY; SESQUITERPENES; TRIGLYCERIDES; WEIGHT LOSS;

EID: 84884905713     PISSN: 19307381     EISSN: 1930739X     Source Type: Journal    
DOI: 10.1002/oby.20356     Document Type: Article

References (24)

1. Flegal KM, Carroll MD, Ogden CL, Curtin LR,. Prevalence and trends in obesity among US adults, 1999-2008. Jama 2010; 303 (3): 235-241.
2. NHLBI/NIDDK. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Bethesda, MD: National Institute of Health; 1998.
3. Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med 2011; 365 (17): 1597-1604.
4. Vetter ML, Wadden TA, Lavenberg J, et al. Relation of health-related quality of life to metabolic syndrome, obesity, depression and comorbid illnesses. Int J Obes (Lond) 2011; 35 (8): 1087-1094.
5. Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring) 2012; 20 (2): 330-342.
6. Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J,. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. Jama 2006; 295 (7): 761-775.
7. Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 2010; 363 (3): 245-256.
8. Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997; 337 (9): 581-588.
9. Yeh JR, Ju R, Brdlik CM, et al. Targeted gene disruption of methionine aminopeptidase 2 results in an embryonic gastrulation defect and endothelial cell growth arrest. Proc Natl Acad Sci U S A 2006; 103 (27): 10379-10384.
10. Rupnick MA, Panigrahy D, Zhang CY, et al. Adipose tissue mass can be regulated through the vasculature. Proc Natl Acad Sci U S A 2002; 99 (16): 10730-10735.
11. Brakenhielm E, Cao R, Gao B, et al. Angiogenesis inhibitor, TNP-470, prevents diet-induced and genetic obesity in mice. Circ Res. 2004; 94 (12): 1579-1588.
12. Kim YM, An JJ, Jin YJ, et al. Assessment of the anti-obesity effects of the TNP-470 analog, CKD-732. J Mol Endocrinol 2007; 38 (4): 455-465.
13. Lijnen HR, Frederix L, Van Hoef B,. Fumagillin reduces adipose tissue formation in murine models of nutritionally induced obesity. Obesity (Silver Spring) 2010; 18 (12): 2241-2246.
14. Sin N, Meng L, Wang MQ, Wen JJ, Bornmann WG, Crews CM,. The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. Proc Natl Acad Sci U S A 1997; 94 (12): 6099-6103.
15. Chun E, Han CK, Yoon JH, Sim TB, Kim YK, Lee KY,. Novel inhibitors targeted to methionine aminopeptidase 2 (MetAP2) strongly inhibit the growth of cancers in xenografted nude model. Int J Cancer 2005; 114 (1): 124-130.
16. Shin SJ, Jeung HC, Ahn JB, et al. A phase I pharmacokinetic and pharmacodynamic study of CKD-732, an antiangiogenic agent, in patients with refractory solid cancer. Invest New Drugs 2010; 28 (5): 650-658.
17. Flint A, Raben A, Blundell JE, Astrup A,. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord 2000; 24 (1): 38-48.
18. Datta B, Majumdar A, Datta R, Balusu R,. Treatment of cells with the angiogenic inhibitor fumagillin results in increased stability of eukaryotic initiation factor 2-associated glycoprotein, p67, and reduced phosphorylation of extracellular signal-regulated kinases. Biochemistry 2004; 43 (46): 14821-14831.
19. Kotzka J, Knebel B, Avci H, et al. Phosphorylation of sterol regulatory element-binding protein (SREBP)-1a links growth hormone action to lipid metabolism in hepatocytes. Atherosclerosis 2010; 213 (1): 156-165.
20. Raghow R, Yellaturu C, Deng X, Park EA, Elam MB,. SREBPs: the crossroads of physiological and pathological lipid homeostasis. Trends Endocrinol Metab 2008; 19 (2): 65-73.
21. Baratta R, Amato S, Degano C, et al. Adiponectin relationship with lipid metabolism is independent of body fat mass: evidence from both cross-sectional and intervention studies. J Clin Endocrinol Metab 2004; 89 (6): 2665-2671.
22. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). Washington DC, USA: National Adademies Press; 2002.
23. Van, Gaal LF, Wauters MA, De Leeuw IH,. The beneficial effects of modest weight loss on cardiovascular risk factors. Int J Obes Relat Metab Disord 1997; 21 (Suppl 1): S5-S9.
24. Pi-Sunyer FX., Short-term medical benefits and adverse effects of weight loss. Ann Intern Med 1993; 119 (7 Pt 2): 722-726.