Carla Chieffo, VMD, PhD, 1 Lawrence A. Frohman, MD, 2 Harry Quandt, BS, 1 Stefanie Decker, MS, 1 Mônica R. Gadelha, MD, PhD 3 1 Endo Pharmaceuticals Inc., Chadds Ford, PA, USA; 2 University of Illinois at Chicago, Chicago, IL, USA; 3 Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil This research was funded by Endo Pharmaceuticals Inc., Chadds Ford, PA, USA. The information concerns an investigational use of a drug that has not been approved by the US Food and Drug Administration Effectiveness and Safety of an Octreotide Hydrogel Implant in Patients With Acromegaly
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Effectiveness and Safety of an Octreotide Hydrogel Implant in Patients With Acromegaly
Effectiveness and Safety of an Octreotide Hydrogel Implant in Patients With Acromegaly. Carla Chieffo, VMD, PhD, 1 Lawrence A. Frohman, MD, 2 Harry Quandt, BS, 1 Stefanie Decker, MS, 1 Mônica R. Gadelha, MD, PhD 3 - PowerPoint PPT Presentation
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Carla Chieffo, VMD, PhD,1 Lawrence A. Frohman, MD,2 Harry Quandt, BS,1 Stefanie Decker, MS,1 Mônica R. Gadelha, MD, PhD3
1Endo Pharmaceuticals Inc., Chadds Ford, PA, USA; 2University of Illinois at Chicago, Chicago, IL, USA; 3Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
This research was funded by Endo Pharmaceuticals Inc., Chadds Ford, PA, USA. The information concerns an investigational use of a drug that has not been approved by the US Food and Drug
Administration
Effectiveness and Safety of an Octreotide Hydrogel Implant in
Patients With Acromegaly
• Approximately 60% of patients with acromegaly achieve biochemical control with octreotide long-acting release (OLAR)1
• OLAR and lanreotide sustained release require monthlyinjections and are associated with large peak-to-trough changes in drug concentrations2
• Drug-release technologies that extend the dosing interval and reduce drug-concentration fluctuations could improve compliance, symptom management, and tolerability
• A subcutaneous octreotide hydrogel implant (OHI) has been developed that provides constant octreotide release for 6 months
Background
1Freda et al. J Clin Endocrinol Metab. 2005;90(8):4465-4473; 2Astruc et al. J Clin Pharmacol. 2005;45(7):836-844
• Objective
– To evaluate the effectiveness and safety of a subcutaneous 52-mg OHI for the treatment of acromegaly
• Study Design
– Phase II, open-label, randomized study at a single Brazilian center• First study to evaluate the effectiveness and safety of OHI
– Acromegaly patients were randomized to receive one or two 52-mg hydrated OHI (60-mg octreotide acetate)• Inserted subcutaneously in the upper arm on day 1 and removed
at month 6
• Visits were scheduled monthly through month 7
Objective and Study Design
Inclusion Exclusion
• Aged ≥18 y with a GH-secreting tumor≥3 mm from the optic chiasm
• Demonstrated response to octreotide
• Serum GH concentration ≥1 ng/mL after OGTT
• Serum IGF-1 concentration ≥30% above upper limit of age-adjusted normal value
• Octreotide discontinuation due to poor tolerability or efficacy
• Previous radiotherapy or recent pituitary surgery <12 weeks before screening
• Dopamine agonist or investigational drug within 2 or 3 months of screening, respectively
• Liver disease, symptomatic cholelithiasis, signs/symptoms of coronary heart disease (≤3 mo of screening), heart failure, drug or alcohol abuse, hypersensitivity to octreotide, pregnancy
GH=growth hormone; IGF-1=insulin-like growth factor–1; OGTT=oral glucose tolerance test
Inclusion/Exclusion Criteria
• Serum IGF-1 concentration assessed monthly using single blood samples (months 1–7)
• Serum GH concentration assessed monthly using – Single blood samples (months 1, 3, 5, 7)
– 5 serial blood samples drawn every 30 minutes for 2 hours (day 1/preinsertion and months 2 and 4)
• OGTT at screening and month 6– GH concentration assessed 0, 30, 60, 90, and 120 minutes after OGTT
• Tumor size and quality of life (QoL) were assessed at screening and month 6
*Mild insertion site pain the day of the implantation procedure; dipyrone was administered, and the pain resolved the next day
• 52-mg OHI provided consistent biochemical control over 6 months and reduced tumor size
• OHI was a safe and effective delivery system for treating patients with acromegaly
• High satisfaction and effectiveness ratings for the OHI
• Phase III studies of the OHI (84 mg) are ongoing
Conclusions
This research was funded by Endo Pharmaceuticals Inc., Chadds Ford, PA, USA The information concerns investigational use of a drug that has not been approved by the US Food and Drug Administration
Author Disclosures
Carla Chieffo: employee of Endo Pharmaceuticals Inc.
Lawrence A. Frohman: consultant to Endo Pharmaceuticals Inc.
Harry Quandt: employee of Endo Pharmaceuticals Inc.
Stefanie Decker: employee of Endo Pharmaceuticals Inc.
Mônica R. Gadelha: nothing to disclose
Presenter: Theodore Danoff, MD, PhD, Vice President of Clinical Development, Endocrinology/Urology, Endo Pharmaceuticals Inc.
• At each monthly visit, suppression of – IGF-1
– GH (single GH and mean 2-h serial GH concentrations)
• After an OGTT at month 6, suppression of GH to <1.0 ng/mL
• Within patient, IGF-1 and GH concentration over the entire 6-month treatment period