Efficacy and Safety of Pasireotide Long Acting Release (LAR) Versus Octreotide LAR or Lanreotide Autogel (ATG) in Patients With Inadequately Controlled Acromegaly (PAOLA)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01137682
First received: May 27, 2010
Last updated: November 13, 2013
Last verified: November 2013
  Purpose

This study will evaluate the efficacy and safety of pasireotide LAR 40 and 60 mg versus octreotide LAR or lanreotide ATG in patients with inadequately controlled acromegaly.


Condition Intervention Phase
Acromegaly
Drug: Pasireotide (SOM230)
Drug: octreotide LAR 30mg
Drug: lanreotide ATG 120mg
Drug: octreotide LAR 30mg or lanreotide ATG 120mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized, Parallel-group Study to Assess the Efficacy and Safety of Double-blind Pasireotide LAR 40 mg and Pasireotide LAR 60 mg Versus Open-label Octreotide LAR or Lanreotide ATG in Patients With Inadequately Controlled Acromegaly

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Measure the mean Growth Hormone (GH) levels and Insulin-like Growth Factor (IGF-1) levels at 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Measure the mean GH levels and IGF-1 levels at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Measure the tumor volume reduction assessed by pituitary MRI at 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Measure the IGF-1 level alone at 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Measure the overall safety and tolerability of pasirotide LAR 40 mg and pasireotide LAR 60 mg [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Measure the health-related quality of life using the AcroQoL instrument [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 190
Study Start Date: July 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pasireotide LAR 40 mg
Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)
Drug: Pasireotide (SOM230)
  • Double-blind pasireotide LAR 40 mg i.m. injection once every 28 ± 2 days for 24 weeks or
  • Double-blind pasireotide LAR 60 mg i.m. injection once every 28 ± 2 days for 24 weeks
Experimental: Pasireotide LAR 60 mg
Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)
Drug: Pasireotide (SOM230)
  • Double-blind pasireotide LAR 40 mg i.m. injection once every 28 ± 2 days for 24 weeks or
  • Double-blind pasireotide LAR 60 mg i.m. injection once every 28 ± 2 days for 24 weeks
Active Comparator: Control arm (octreotide or lanreotide)

If a patient is randomized to the open label arm the investigator will either:

  • be instructed to contact a Novartis delegate to initiate shipment of either octreotide LAR 30 mg or lanreotide ATG 120 mg from a Novartis or designee depot to the site, or
  • continue to dispense either octreotide LAR 30 mg or lanreotide ATG 120 mg available at the institution to the patient if permitted by local regulations.
Drug: octreotide LAR 30mg
In an open-label, active control arm, continue on the same treatment with octreotide LAR 30 mg every 28 ± 2 days as received for at least 6 months prior to randomization
Drug: lanreotide ATG 120mg
In an open-label, active control arm, continue on the same treatment with lanreotide ATG 120 mg every 28 ± 2 days as received for at least 6 months prior to randomization
Drug: octreotide LAR 30mg or lanreotide ATG 120mg

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with written informed consent prior to any study related activity
  2. Patients with inadequately controlled acromegaly as defined by a mean GH concentration of a 5-point profile over a 2-hour period > 2.5 µg/L and sex- and age-adjusted IGF-1 > 1.3 x upper limit of normal (ULN)
  3. Patients treated with maximum indicated doses of octreotide LAR or lanreotide ATG for at least 6 months prior to visit 1 (screening). The maximum indicated dose for octreotide LAR is 30mg and for lanreotide ATG is 120 mg
  4. Patients with diagnosis of pituitary micro- or macro adenoma. Patients can have been previously submitted to surgery

Exclusion Criteria:

  1. Patients who have received pasireotide (SOM 230) prior to enrolment
  2. Concomitant treatment with Growth Hormone Receptor (GHR)-antagonist or dopamine agonists unless concomitant treatment was discontinued 8 weeks prior to visit 1 (screening)(8 weeks wash out period). Such patients must have been treated with octreotide LAR 30 mg or lanreotide ATG 120 mg monotherapy continuously for a minimum of 6 months prior to starting combination therapy and they should have been inadequately controlled on monotherapy.
  3. Patients with compression of the optic chiasm causing acute clinically significant visual field defects
  4. Patients who require a surgical intervention for relief of any sign or symptom associated with tumor compression
  5. Patients who have received pituitary irradiation within 10 years prior to visit 1 (screening).
  6. Patients who have undergone major surgery/surgical therapy for any cause within 4 weeks prior to visit 1 (screening).
  7. Patients who are hypothyroid and not adequately treated with a stable dose of thyroid hormone replacement therapy

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01137682

  Show 62 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01137682     History of Changes
Other Study ID Numbers: CSOM230C2402, 2009-016722-13, EUDRACT 2009-016722-13
Study First Received: May 27, 2010
Last Updated: November 13, 2013
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Belgium: Ministry of Social Affairs, Public Health and the Environment
Brazil: National Health Surveillance Agency
Canada: Health Canada
Colombia: Institutional Review Board
France: Ministry of Health
Germany: Ministry of Health
Israel: Ministry of Health
Italy: Ministry of Health
Norway: Norwegian Medicines Agency
Poland: Ministry of Health
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Saudi Arabia: Ministry of Health
Spain: Ministry of Health and Consumption
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Mexico: Ministry of Health

Keywords provided by Novartis:
Acromegaly
hormone disorder
growth hormone
insulin like growth factor-1
pituitary tumor

Additional relevant MeSH terms:
Acromegaly
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases
Hyperpituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Octreotide
Lanreotide
Angiopeptin
Somatostatin
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents
Cardiovascular Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 20, 2014