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

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ClinicalTrials.gov Identifier: NCT02354508
Recruitment Status : Completed
First Posted : February 3, 2015
Results First Posted : December 4, 2019
Last Update Posted : December 10, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This is a phase IIIb multicenter, open-label; single arm study to evaluate the efficacy and safety of pasireotide LAR 40 mg and 60 mg in patients with inadequately controlled acromegaly with maximal approved doses of first generation somatostatin analogues. The study will enroll inadequately controlled patients by high doses (maximal approved) of first-generation somatostatin analogues given for at least 3 months. Patients will receive pasireotide LAR 40 mg or 60 mg during the 36 week core study phase. Patients who have completed all visits of core phase and have completed all the assessments at the core phase completion visit can move into the 32-week extension phase. Patients can continue with study treatment until pasireotide LAR is commercially available and reimbursed in their respective country or until the end of the extension phase whichever occurs first.

Condition or disease Intervention/treatment Phase
Acromegaly Drug: Pasireotide LAR Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 123 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : March 31, 2015
Actual Primary Completion Date : January 8, 2018
Actual Study Completion Date : September 27, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Pasireotide

Arm Intervention/treatment
Experimental: Pasireotide LAR
Patients who qualify for the core phase of the study will be treated with pasireotide LAR 40 mg initially. Patients not achieving biochemical control can be up-titrated to pasireotide LAR 60 mg.
Drug: Pasireotide LAR
Pasireotide 40 mg and 60 mg. Pasireotide 20 mg which was allowed for dose decrease in case of adverse event.
Other Name: SOM230




Primary Outcome Measures :
  1. 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 ]
    Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36.

  2. 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 ]
    Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36, for participants who had been up-titrated with pasireotide LAR 60 mg.

  3. Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 [ Time Frame: Wek 36 ]
    Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36.

  4. Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 [ Time Frame: Week 36 ]
    Percentage of patients who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36, by previous treatment, type of therapy and overall.

  5. 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 ]
    Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36, overall by baseline diabetic status.

  6. 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 ]
    Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36, by previous treatment and overall - last observation carried forward (LOCF)


Secondary Outcome Measures :
  1. Core Phase: Change in Mean Growth Hormone (GH) Values From Baseline to Week 36 [ Time Frame: Baseline, week 36 ]
    Core phase - Changes in mean GH from study baseline to week 36.

  2. Core Phase: Change in Standardized IGF-1 Values From Baseline to Week 36 [ Time Frame: Baseline, week 36 ]
    Core phase - Changes in standardized IGF-1 from study baseline to week 36.

  3. Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN [ Time Frame: Week 12, Week 24, Week 36 ]
    Percentage of participants achieving GH <1 μg/L and IGF-1 <ULN at weeks 12 and 24 overall and by GH level at screening.

  4. Core Phase: Percentage of Participants With IGF-1 <ULN Overall by GH Level at Screening [ Time Frame: Weeks 12, 24 & 36 ]
    Percentage of participants achieving IGF-1 <ULN at weeks 12, 24 & 36.

  5. Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Overall by Baseline Diabetic Status [ Time Frame: Weeks 12, 24 & 36 ]
    Core phase - Percentage of patients achieving GH <1μg/L at week 12, 24, 36 overall and by GH level at screening.

  6. Core Phase: Change From Baseline in Scores as Measured by Acromegaly Quality of Life (AcroQoL) [ Time Frame: Baseline, Weeks 12, 24 & 36 ]
    Evaluation of effect of pasireotide LAR on Health Related Quality of Life (HRQoL) was assessed using AcroQoL, an acromegaly-specific quality of life instrument. The AcroQol instrument is comprised of 22 questions divided into two scales: one evaluating physical aspects (8 items) and the other that addresses psychological aspects (14 items). The psychological scale can also be further divided into subscale that evaluates physical appearance and the other subscale focused on the impact of the disease on personal relationships of the patient (7 items each). Each of the questions has a 5-item Likert scale. For each dimension the scores range from 0-4 with 0 being the lowest impact and 4 being the most severe.

  7. Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms [ Time Frame: Weeks 12, 24 & 36 ]
    Symptoms of acromegaly were collected at various visits. The measurement was to be provided on a scale of 1-15 including half sizes. Investigators asked the participants to score the following symptoms of acromegaly: headache, fatigue, perspiration, paresthesias, osteoarthralgia according to a five-point score scale (0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe).

  8. Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline [ Time Frame: Weeks 12, 24 & 36 ]
    Symptoms of acromegaly were collected at various visits. The measurement was to be provided on a scale of 1-15 including half sizes. Investigators asked the participants to score the following symptoms of acromegaly: headache, fatigue, perspiration, paresthesias, osteoarthralgia according to a five-point score scale (0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe).

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

    Evaluation of effect of pasireotide LAR on health status, measured by EQ-5D-5L, a valid and reliable instrument for measuring general health status. The EQ-5D-5L consists of 2 pages - the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20-cm vertical, visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine'. This scale is numbered from 0 to 100. 100 means the best health you can imagine.

    0 means the worst health you can imagine.


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

    Evaluation of effect of pasireotide LAR on health status, measured by EQ-5D-5L, a valid and reliable instrument for measuring general health status. The EQ-5D-5L consists of 2 pages - the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20-cm vertical, visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine'. This scale is numbered from 0 to 100. 100 means the best health you can imagine.

    0 means the worst health you can imagine.


  11. 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 ]
    Percentage of patients achieving IGF-1 <ULN at weeks 48, 60 & 72 for participants with up-titrated to Pasireotide LAR 60 mg mg

  12. 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 ]
    Percentage of participants achieving IGF-1 <ULN at week 46, 60 and 72 overall by baseline diabetic status

  13. 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 ]
    Percentage of patients achieving GH <1 μg/L and IGF-1 <ULN at week 48 by treatment with pasireotide LAR alone or with concomitant medications used to treat acromegaly

  14. Extension Phase: Change From Baseline in Scores as Measured by Acromegaly Quality of Life (AcroQoL) [ Time Frame: Baseline, Weeks 48, 60 & 72 ]
    Evaluation of effect of pasireotide LAR on Health Related Quality of Life (HRQoL) was assessed using AcroQoL, an acromegaly-specific quality of life instrument. The AcroQol instrument is comprised of 22 questions divided into two scales: one evaluating physical aspects (8 items) and the other that addresses psychological aspects (14 items). The psychological scale can also be further divided into subscale that evaluates physical appearance and the other subscale focused on the impact of the disease on personal relationships of the patient (7 items each). Each of the questions has a 5-item Likert scale. For each dimension the scores range from 0-4 with 0 being the lowest impact and 4 being the most severe.

  15. Extension Phase: Percentage of Participants Reporting Levels 1 - 5 by Dimensions of Acromegaly Symptoms [ Time Frame: Weeks 48, 60 & 72 ]
    Symptoms of acromegaly were collected at various visits. The measurement was to be provided on a scale of 1-15 including half sizes. Investigators asked the participants to score the following symptoms of acromegaly: headache, fatigue, perspiration, paresthesias, osteoarthralgia according to a five-point score scale (0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe).

  16. 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 ]
    Symptoms of acromegaly were collected at various visits. The measurement was to be provided on a scale of 1-15 including half sizes. Investigators asked the participants to score the following symptoms of acromegaly: headache, fatigue, perspiration, paresthesias, osteoarthralgia according to a five-point score scale (0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe).

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

    Evaluation of effect of pasireotide LAR on health status, measured by EQ-5D-5L, a valid and reliable instrument for measuring general health status. The EQ-5D-5L consists of 2 pages - the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20-cm vertical, visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine'. This scale is numbered from 0 to 100. 100 means the best health you can imagine.

    0 means the worst health you can imagine.


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

    Evaluation of effect of pasireotide LAR on health status, measured by EQ-5D-5L, a valid and reliable instrument for measuring general health status. The EQ-5D-5L consists of 2 pages - the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20-cm vertical, visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine'. This scale is numbered from 0 to 100. 100 means the best health you can imagine.

    0 means the worst health you can imagine.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02354508


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] August 5, 2015
Statistical Analysis Plan  [PDF] October 6, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02354508    
Other Study ID Numbers: CSOM230C2413
2014-002630-31 ( EudraCT Number )
First Posted: February 3, 2015    Key Record Dates
Results First Posted: December 4, 2019
Last Update Posted: December 10, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

URL: http://www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
acromegaly
GH
IGF-1
pasireotide LAR
SOM230
first generation
somatostatin analogues
growth disorder
gigantism
Pituitary adenoma
pituitary gigantism
Additional relevant MeSH terms:
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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
Pasireotide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs