Pasireotide in Patients With Acromegaly Inadequately Controlled With First Generation Somatostatin Analogues

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02354508
• Date of registration: 29/01/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Pasireotide in Patients With Acromegaly Inadequately Controlled With First Generation Somatostatin Analogues
• Scientific title: A Phase IIIb Multicenter, Open-label, Single Arm Study to Evaluate the Efficacy and Safety of Pasireotide in Patients With Acromegaly Inadequately Controlled With First Generation Somatostatin Analogues
• Date of first enrolment: March 31, 2015
• Target sample size: 123
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02354508
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Belgium, Brazil, Bulgaria, China, Colombia, France, Hungary, Italy, Malaysia, Mexico, Portugal, Romania, Turkey, United Kingdom

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria:

- Written informed consent

- Male and female patients =18 years

- Patients with confirmed diagnosis of inadequately controlled acromegaly (mean GH
concentration =1 µg/L and sex- and age-adjusted IGF-1 >1.3 x ULN)

- Patients treated with octreotide LAR (30 mg or 40 mg) or lanreotide ATG (120 mg)
monotherapy for at least 3 months prior to screening

Exclusion Criteria:

- Concomitant treatment with other medications reducing GH and or IGF-1, unless
discontinued 3 months prior to screening

- Patients with compression of the optic chiasm requiring surgical intervention

- Diabetic patients with HbA1c >8% at screening

- Patients who are hypothyroid and not on adequate replacement therapy

- Patients with symptomatic cholelithiasis and acute or chronic pancreatitis

- Patients with clinically significant valvular disease

- Patients with risk factors for torsade de pointes (TdP)

- Hypokalaemia, hypomagnesaemia, uncontrolled hypothyroidism, family history of long QT
syndrome or concomitant medications with known risk of TdP

- Patients with congestive heart failure (NYHA Class III or IV), unstable angina,
sustained ventricular tachycardia, clinically significant bradycardia, advanced heart
block, history of acute MI less than one year prior to study entry or clinically
significant impairment in cardiovascular function.

- Concomitant disease(s) that could prolong the QT interval such as autonomic neuropathy
(caused by diabetes or Parkinson's disease), HIV, cirrhosis, uncontrolled
hypothyroidism or cardiac failure

- Patients with liver disease or ALT/AST > 2.0 X ULN, serum bilirubin >2.0 X ULN -
Presence of Hepatitis B surface antigen or Hepatitis C antibody test

- Patients with serum creatinine >2.0 X ULN

- Patients with WBC <3 X 109/L; Hb 90% < LLN; PLT <100 X 109/L

- Patients with active or suspected acute or chronic uncontrolled infection

- Patients who have undergone major surgery/surgical therapy within 4 weeks prior to
screening

- Patients with active malignant disease within the last five years (with the exception
of basal cell carcinoma or carcinoma in situ of the cervix)

- Patients with abnormal coagulation (PT and/or APTT elevated by 30% above normal
limits) or patients receiving anticoagulants that affect PT (prothrombin time) or APTT
(activated partial thromboplastin time)

- History of syncope or family history of idiopathic sudden death

- History of immunocompromise, including a positive HIV test result (ELISA and Western
blot)

- Known hypersensitivity to somatostatin analogues or any other component of pasireotide
LAR

- Patients who have a history of alcohol or drug abuse in the 6 month period prior to
receiving pasireotide

- Patients who have given a blood donation (of 400 ml or more) within 2 months before
receiving pasireotide

- Patients who have participated in any clinical investigation with an investigational
drug within 1 month prior to dosing

- Patients with any current or prior medical condition interfering with the conduct of
the study or the evaluation of the study results

- Patients with a history of non-compliance to medical regimens or who are considered
potentially unreliable or will be unable to complete the entire study.

- Sexually active males unless they use a condom during intercourse while taking drug
and for 3 months following last dose of pasireotide

- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test

- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and 3 months following the last dose of pasireotide.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Acromegaly

Intervention(s)

Drug: Pasireotide LAR

Primary Outcome(s)

Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 [Time Frame: Wek 36]

Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 for Participants Up-titrated to Pasireotide LAR 60 mg [Time Frame: Week 36]

Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 by Previous Treatment and Overall - LOCF [Time Frame: Week 36]

Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 [Time Frame: Week 36]

Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 by Previous Treatment and Overall [Time Frame: Week 36]

Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 Overall by Baseline Diabetic Status [Time Frame: Week 36]

Secondary Outcome(s)

Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms [Time Frame: Weeks 12, 24 & 36]

Extension Phase: Change From Baseline in Scores as Measured by Acromegaly Quality of Life (AcroQoL) [Time Frame: Baseline, Weeks 48, 60 & 72]

Core Phase: Change in Mean Growth Hormone (GH) Values From Baseline to Week 36 [Time Frame: Baseline, week 36]

Core Phase: Percentage of Participants With IGF-1 [Time Frame: Weeks 12, 24 & 36]

Core Phase: Change From Baseline in EQ-5D-5L Index Scores [Time Frame: Baseline, Weeks 12, 24 & 36]

Core Phase: Percentage of Participants With Mean GH <1 µg/L and IGF-1 [Time Frame: Week 12, Week 24, Week 36]

Extension Phase: Percentage of Participants With Mean GH < 1 µg/L at Weeks 48, 60, 72 and Overall, Pasireotide Montherapy and Pasireotide With Concomittant Medication and by GH Level at Screening [Time Frame: Weeks 48, 60, 72]

Extension (Ext.) Phase: Percentage of Participants With Acromegaly Shift Symptoms From Extension Baseline to Most Extreme Post-extension Baseline [Time Frame: Weeks 48, 60 & 72]

Extension Phase: Percentage of Participants Reporting Levels 1 - 5 by Dimensions of Acromegaly Symptoms [Time Frame: Weeks 48, 60 & 72]

Extension Phase: Change From Baseline in EQ-5D-5L VAS Assessment [Time Frame: Baseline, Weeks 48, 60 & 72]

Core Phase: Change From Baseline in EQ-5D-5L VAS Assessment [Time Frame: Baseline, Weeks 12, 24 & 36]

Core Phase: Change From Baseline in Scores as Measured by Acromegaly Quality of Life (AcroQoL) [Time Frame: Baseline, Weeks 12, 24 & 36]

Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline [Time Frame: Weeks 12, 24 & 36]

Core Phase: Percentage of Participants With Mean GH <1 µg/L and IGF-1 [Time Frame: Weeks 12, 24 & 36]

Core Phase: Change in Standardized IGF-1 Values From Baseline to Week 36 [Time Frame: Baseline, week 36]

Extension Phase: Change From Baseline in EQ-5D-5L Index Scores [Time Frame: Baseline, Weeks 48, 60 & 72]

Extension Phase: Percentage of Participants With Mean GH < 1 µg/L and IGF-1 < ULN at Weeks 48, 60 & 72 (Up-titrated to Pasireotide LAR 60 mg) [Time Frame: Weeks 48, 60 & 72]

Extension Phase: Percentage of Participants With Mean GH < 1 µg/L and IGF-1 < ULN at Weeks 48, 60 and 72 (Overall by Baseline Diabetic Status) [Time Frame: Weeks 48, 60, 72]

Secondary ID(s)

CSOM230C2413

2014-002630-31

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 04/12/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02354508