Clinical Trial: Pasireotide in Patients With Acromegaly Inadequately Controlled With First Generation Somatostatin Analogues

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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 Ge

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.

Detailed 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 doses of first generation somatostatin analogues. The study will enroll inadequately controlled patients by high doses of first-generation somatostatin analogues given for at least 3 months.

Patients will be categorized into two groups. Group 1 consists of patients treated with octreotide LAR 30 mg from countries where octreotide LAR 40mg is approved for the treatment of acromegaly at the time of screening. These patients will start a 3-months run-in phase to receive 40mg octreotide before being considered eligible to enter the core treatment phase. After 3 months of treatment have been completed, and prior to the fourth injection a mean GH and IGF-1 will be assessed. Patients who are achieving biochemical control will be considered a screen failure and they will not qualify for the core phase of the study. They will continue treatment with octreotide LAR 40 mg outside the frame of this study.

Group 2 consists of patients treated with octreotide LAR 30 mg from countries where octreotide 40mg is NOT yet approved at the time of screening. This group also includes patients already treated with octreotide LAR 40 mg or lanreotide ATG 120 mg. Patients should have been treated with the first generation SSAs for at least 3 months prior to screening. Eligible patients can directly enter the core treatment phase of the study. A run-in phase is not required for this patient population.

In the core treatment phase patients will start treatment with pasireotide LAR 40 mg every 4 weeks. At week 12, the mean GH value and IGF-1value will be assessed. Patients who have not achieved biochemical c
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Patients achieving GH <1μg/L and IGF-1 <ULN [ Time Frame: week 36 ]

Proportion of patients who achieve biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36.


Original Primary Outcome:

  • Patients achieving GH <1μg/L and IGF-1 <ULN [ Time Frame: week 36 ]
    Proportion of patients who achieve biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36.
  • Patients achieving GH <1μg/L and IGF-1 <ULN depending on initial GH level [ Time Frame: week 36 ]
    Supportive analysis for primary outcome measure: Proportion of patients achieving GH <1μg/L and IGF-1 <ULN at week 36 in patients having GH level at screening between 1 μg/L and 2.5 μg/L, and in patients having GH level at screening >2.5 μg/L


Current Secondary Outcome:

  • Change in mean GH level [ Time Frame: baseline, week 36 ]
    Core phase - Changes in mean GH from study baseline to week 36.
  • Change in standardized IGF-1 level [ Time Frame: baseline, week 36 ]
    Core phase - Changes in standardized IGF-1 from study baseline to week 36.
  • Patients achieving GH <1μg/L and IGF-1 <ULN [ Time Frame: week 12 ]
    Core phase - Proportion of patients achieving GH <1μg/L and IGF-1 <ULN at week 12 overall and by GH level at screening.
  • Patients achieving GH <1μg/L and IGF-1 <ULN [ Time Frame: week 24 ]
    Core phase - Proportion of patients achieving GH <1μg/L and IGF-1 <ULN at week 24 overall and by GH level at screening.
  • Patients achieving GH <1μg/L overall and by initial GH level [ Time Frame: week 12 ]
    Core phase - Proportion of patients achieving GH <1μg/L at week 12 overall and by GH level at screening.
  • Patients achieving GH <1μg/L overall and by initial GH level [ Time Frame: week 24 ]
    Core phase - Proportion of patients achieving GH <1μg/L at week 24 overall and by GH level at screening.
  • Patients achieving GH <1μg/L overall and by initial GH level [ Time Frame: week 36 ]
    Core phase - Proportion of patients achieving GH <1μg/L at week 36 overall and by GH level at screening.
  • Patients achieving IGF-1 <ULN [ Time Frame: week 12 ]
    Core phase - Proportion of patients achieving IGF-1 <ULN at week 12.
  • Patients achieving IGF-1 <ULN [ Time Frame: week 24 ]
    Core phase - Proportion of patients achieving IGF-1 <ULN at week 24.
  • Patients achieving IGF-1 <ULN [ Time Frame: week 36 ]
    Core phase - Proportion of patients achieving IGF-1 <ULN at week 36.
  • Tolerability and safety profile of pasireotide LAR [ Time Frame: Study enrollment to end of safety follow-up period ]
    Core phase - Toxicity will be assessed using the National Cancer Institute-Common Toxicology Criteria Adverse Events version 4 (NCI-CTCAE v.4.03) and for laboratory assessments that include biochemistry, hematology, urinalysis; special safety assessments that include the regular monitoring and recording of blood glucose, insulin, HbA1c, GH and IGF-1, thyroid and liver function tests, gallbladder examinations and ECGs. Concomitant medications/Significant nondrug therapies will be assessed from study enrollment until the safety follow-up.
  • Evaluation of effect of pasireotide LAR on HRQoL and signs and symptoms of acromegaly [ Time Frame: week 12 ]
    Core phase - Change in scores as measured by AcroQoL, EQ-5D- 5L and signs and symptoms of acromegaly from baseline to week 12
  • Evaluation of effect of pasireotide LAR on HRQoL and signs and symptoms of acromegaly [ Time Frame: week 24 ]
    Core phase - Change in scores as measured by AcroQoL, EQ-5D- 5L and signs and symptoms of acromegaly from baseline to week 24
  • Evaluation of effect of pasireotide LAR on HRQoL and signs and symptoms of acromegaly [ Time Frame: week 36 ]
    Core phase - Change in scores as measured by AcroQoL, EQ-5D- 5L and signs and symptoms of acromegaly from baseline to week 36
  • Patients achieving IGF-1 <ULN [ Time Frame: week 48 ]
    Extension phase - Proportion of patients achieving IGF-1 <ULN at week 48
  • Patients achieving IGF-1 <ULN [ Time Frame: week 60 ]
    Extension phase - Proportion of patients achieving IGF-1 <ULN at week 60
  • Patients achieving IGF-1 <ULN [ Time Frame: week 72 ]
    Extension phase - Proportion of patients achieving IGF-1 <ULN at week 72
  • Patients achieving GH <1 μg/L and IGF-1 <ULN with pasireotide alone or concomitant acromegaly medications [ Time Frame: week 48 ]
    Extension phase - Proportion 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
  • Patients achieving GH <1 μg/L and IGF-1 <ULN with pasireotide alone or concomitant acromegaly medications [ Time Frame: week 60 ]
    Extension phase - Proportion of patients achieving GH

    Original Secondary Outcome: Same as current

    Information By: Novartis

    Dates:
    Date Received: January 29, 2015
    Date Started: March 31, 2015
    Date Completion: August 6, 2018
    Last Updated: May 17, 2017
    Last Verified: May 2017