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

Novartis

Status and phase: Completed; Phase 3

Conditions: Acromegaly

Treatments: Drug: lanreotide ATG 120mg; Drug: octreotide LAR 30mg; Drug: Pasireotide

Study type: Interventional

Funder types: Industry

Identifiers

NCT01137682

EUDRACT 2009-016722-13 (Registry Identifier)

CSOM230C2402

Details and patient eligibility

About

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.

Enrollment: 198 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with written informed consent prior to any study related activity
2. Patients who had 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 who had been 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 was 30mg and for lanreotide ATG iwas120 mg
4. Patients who had a diagnosis of pituitary micro- or macro adenoma. Patients could have been previously submitted to surgery
5. Patients who completed the 24-week treatment period in core according to the requirements of the core study protocol or corresponding amendments could enter extension

Exclusion criteria

1. Patients who had 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 who had compression of the optic chiasm causing acute clinically significant visual field defects
4. Patients who required a surgical intervention for relief of any sign or symptom associated with tumor compression
5. Patients who had received pituitary irradiation within 10 years prior to visit 1 (screening).
6. Patients who had undergone major surgery/surgical therapy for any cause within 4 weeks prior to visit 1 (screening).
7. Patients who were hypothyroid and not adequately treated with a stable dose of thyroid hormone replacement therapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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198 participants in 3 patient groups

Pasireotide LAR 40 mg

Experimental group

Description:

Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)

Treatment:

Drug: Pasireotide

Pasireotide LAR 60 mg

Experimental group

Description:

Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)

Treatment:

Drug: Pasireotide

Control arm (octreotide or lanreotide)

Active Comparator group

Description:

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.

Treatment:

Drug: octreotide LAR 30mg

Drug: lanreotide ATG 120mg