Acromegaly Clinical Trial
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
Verified date | December 2019 |
Source | Novartis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 123 |
Est. completion date | September 27, 2018 |
Est. primary completion date | January 8, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
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. |
Country | Name | City | State |
---|---|---|---|
Argentina | Novartis Investigative Site | Caba | Buenos Aires |
Argentina | Novartis Investigative Site | Caba | Buenos Aires |
Argentina | Novartis Investigative Site | Mar del Plata | Buenos Aires |
Belgium | Novartis Investigative Site | Bruxelles | |
Belgium | Novartis Investigative Site | Edegem | |
Belgium | Novartis Investigative Site | Leuven | |
Brazil | Novartis Investigative Site | Rio de Janeiro | RJ |
Bulgaria | Novartis Investigative Site | Sofia | |
China | Novartis Investigative Site | Beijing | Beijing |
China | Novartis Investigative Site | Chengdu | Sichuan |
China | Novartis Investigative Site | Guangzhou | Guangdong |
Colombia | Novartis Investigative Site | Bogota | |
Colombia | Novartis Investigative Site | Floridablanca | Santander |
France | Novartis Investigative Site | Angers cedex 09 | |
France | Novartis Investigative Site | Besancon cedex | |
France | Novartis Investigative Site | Bron Cedex | |
France | Novartis Investigative Site | Nimes Cedex | |
France | Novartis Investigative Site | Reims | |
France | Novartis Investigative Site | Rouen | |
France | Novartis Investigative Site | St Herblain | |
France | Novartis Investigative Site | Vandoeuvre les Nancy | |
Hungary | Novartis Investigative Site | Budapest | |
Hungary | Novartis Investigative Site | Szeged | HUN |
Italy | Novartis Investigative Site | Ancona | AN |
Italy | Novartis Investigative Site | Genova | GE |
Italy | Novartis Investigative Site | Milano | MI |
Italy | Novartis Investigative Site | Milano | MI |
Italy | Novartis Investigative Site | Napoli | |
Italy | Novartis Investigative Site | Padova | PD |
Italy | Novartis Investigative Site | Palermo | PA |
Italy | Novartis Investigative Site | Pisa | PI |
Italy | Novartis Investigative Site | Torino | TO |
Malaysia | Novartis Investigative Site | Pulau Pinang | |
Malaysia | Novartis Investigative Site | Wilayah Persekutuan | |
Mexico | Novartis Investigative Site | Durango | |
Mexico | Novartis Investigative Site | Guadalajara | Jalisco |
Mexico | Novartis Investigative Site | México | Distrito Federal |
Portugal | Novartis Investigative Site | Lisboa | |
Portugal | Novartis Investigative Site | Porto | |
Portugal | Novartis Investigative Site | Porto | |
Romania | Novartis Investigative Site | Bucuresti | |
Romania | Novartis Investigative Site | Iasi | |
Turkey | Novartis Investigative Site | Ankara | |
Turkey | Novartis Investigative Site | Istanbul | TUR |
Turkey | Novartis Investigative Site | Izmir | |
Turkey | Novartis Investigative Site | Kocaeli | |
Turkey | Novartis Investigative Site | Pendik / Istanbul | |
United Kingdom | Novartis Investigative Site | London | |
United Kingdom | Novartis Investigative Site | Nottingham | |
United Kingdom | Novartis Investigative Site | Plymouth |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
Argentina, Belgium, Brazil, Bulgaria, China, Colombia, France, Hungary, Italy, Malaysia, Mexico, Portugal, Romania, Turkey, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 by Previous Treatment and Overall | Percentage of participants who achieved biochemical control defined as GH <1µg/L and IGF-1 Week 36 |
| |
Primary | 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 | Percentage of participants who achieved biochemical control defined as GH <1µg/L and IGF-1 Week 36 |
| |
Primary | Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 | Percentage of participants who achieved biochemical control defined as GH <1µg/L and IGF-1 Wek 36 |
| |
Primary | Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 | Percentage of patients who achieved biochemical control defined as GH <1µg/L and IGF-1 Week 36 |
| |
Primary | Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 Overall by Baseline Diabetic Status | Percentage of participants who achieved biochemical control defined as GH <1µg/L and IGF-1 Week 36 |
| |
Primary | Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 by Previous Treatment and Overall - LOCF | Percentage of participants who achieved biochemical control defined as GH <1µg/L and IGF-1 Week 36 |
| |
Secondary | Core Phase: Change in Mean Growth Hormone (GH) Values From Baseline to Week 36 | Core phase - Changes in mean GH from study baseline to week 36. | Baseline, week 36 | |
Secondary | Core Phase: Change in Standardized IGF-1 Values From Baseline to Week 36 | Core phase - Changes in standardized IGF-1 from study baseline to week 36. | Baseline, week 36 | |
Secondary | Core Phase: Percentage of Participants With Mean GH <1 µg/L and IGF-1 <ULN | Percentage of participants achieving GH <1 µg/L and IGF-1 Week 12, Week 24, Week 36 |
| |
Secondary | Core Phase: Percentage of Participants With IGF-1 <ULN Overall by GH Level at Screening | Percentage of participants achieving IGF-1 Weeks 12, 24 & 36 |
| |
Secondary | Core Phase: Percentage of Participants With Mean GH <1 µg/L and IGF-1 <ULN Overall by Baseline Diabetic Status | Core phase - Percentage of patients achieving GH <1µg/L at week 12, 24, 36 overall and by GH level at screening. | Weeks 12, 24 & 36 | |
Secondary | Core Phase: Change From Baseline in Scores as Measured by Acromegaly Quality of Life (AcroQoL) | 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. | Baseline, Weeks 12, 24 & 36 | |
Secondary | Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms | 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). | Weeks 12, 24 & 36 | |
Secondary | Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline | 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). | Weeks 12, 24 & 36 | |
Secondary | Core Phase: Change From Baseline in EQ-5D-5L Index Scores | 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. |
Baseline, Weeks 12, 24 & 36 | |
Secondary | Core Phase: Change From Baseline in EQ-5D-5L VAS Assessment | 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. |
Baseline, Weeks 12, 24 & 36 | |
Secondary | 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) | Percentage of patients achieving IGF-1 Weeks 48, 60 & 72 |
| |
Secondary | 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) | Percentage of participants achieving IGF-1 Weeks 48, 60, 72 |
| |
Secondary | 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 | Percentage of patients achieving GH <1 µg/L and IGF-1 Weeks 48, 60, 72 |
| |
Secondary | Extension Phase: Change From Baseline in Scores as Measured by Acromegaly Quality of Life (AcroQoL) | 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. | Baseline, Weeks 48, 60 & 72 | |
Secondary | Extension Phase: Percentage of Participants Reporting Levels 1 - 5 by Dimensions of Acromegaly Symptoms | 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). | Weeks 48, 60 & 72 | |
Secondary | Extension (Ext.) Phase: Percentage of Participants With Acromegaly Shift Symptoms From Extension Baseline to Most Extreme Post-extension Baseline | 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). | Weeks 48, 60 & 72 | |
Secondary | Extension Phase: Change From Baseline in EQ-5D-5L Index Scores | 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. |
Baseline, Weeks 48, 60 & 72 | |
Secondary | Extension Phase: Change From Baseline in EQ-5D-5L VAS Assessment | 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. |
Baseline, Weeks 48, 60 & 72 |
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