Phase II Study of Subcutaneous Inj. Depot of Octreotide in Patients With Acromegaly and Neuroendocrine Tumours (NETs)

Study Overview
=================
Brief Summary
-----------------
This is a Phase II, open-label multicentre, randomised study to assess the PK, PD, efficacy, and safety of two dosing regimens of CAM2029 in adult patients with acromegaly or a functional, well-differentiated NET, with carcinoid symptoms.

Detailed Description
-----------------
This is a Phase II, open-label multicentre, randomised study to assess the PK, PD, efficacy, and safety of two dosing regimens of CAM2029 in adult patients with acromegaly or a functional, well-differentiated NET, with carcinoid symptoms, treated for at least 2 months with Sandostatin LAR at doses of 10 mg, 20 mg, or 30 mg before the start of the Sandostatin LAR Last Dose Assessment Phase (Day -28).

Official Title
-----------------
A Phase II, Open-label, Multicentre, Randomised Study of the Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of CAM2029 in Patients With Acromegaly and Neuroendocrine Tumours (NETs) Previously Treated With Sandostatin® LAR®

Conditions
-----------------
Acromegaly, Neuroendocrine Tumors

Intervention / Treatment
-----------------
* Drug: octreotide FluidCrystal® injection depot


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Acromegaly: Male or female patients ≥18 years of age Acromegaly currently treated with Sandostatin LAR NET: Male or female patients ≥18 years of age Functional, well-differentiated (Grade 1 or Grade 2) NET with symptoms of carcinoid syndrome (number of bowel movements and/or flushing) Currently treated with Sandostatin LAR for symptom control Exclusion Criteria: Acromegaly: Inadequate bone marrow function Abnormal coagulation or chronic treatment with warfarin or coumarin derivates Impaired liver, cardiac and/or renal function Known gallbladder, bile duct disease or pancreatitis Diabetes with poorly controlled blood glucose levels despite adequate therapy Hypothyroidisms not adequately treated NET: Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, insulinoma, glucagonoma, gastrinoma, goblet cell carcinoid, typical and atypical lung carcinoids, large cell neuroendocrine carcinoma and small cell carcinoma Carcinoid syndrome refractory to treatment with conventional doses of somatostatin analogues (SSAs) Inadequate bone marrow function Abnormal coagulation or chronic treatment with warfarin or coumarin derivates Impaired liver, cardiac and/or renal function Known gallbladder, bile duct disease or pancreatitis Short-bowel syndrome Diabetics with poorly controlled blood glucose levels despite adequate therapy Hypothyroidism, not adequately treated

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAM2029 10 mg (NET)<br>CAM2029 (octreotide FluidCrystal® injection depot) 10 mg, subcutaneous injection every two weeks | Drug: octreotide FluidCrystal® injection depot<br> <br> * Other names: CAM2029;|
| Experimental: CAM2029 20 mg (NET)<br>CAM2029 (octreotide FluidCrystal® injection depot) 20 mg, subcutaneous injection once monthly | Drug: octreotide FluidCrystal® injection depot<br> <br> * Other names: CAM2029;|
| Experimental: CAM2029 10 mg (Acromegaly)<br>CAM2029 (octreotide FluidCrystal® injection depot) 10 mg, subcutaneous injection every two weeks | Drug: octreotide FluidCrystal® injection depot<br> <br> * Other names: CAM2029;|
| Experimental: CAM2029 20 mg (Acromegaly)<br>CAM2029 (octreotide FluidCrystal® injection depot) 20 mg, subcutaneous injection once monthly | Drug: octreotide FluidCrystal® injection depot<br> <br> * Other names: CAM2029;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) AUC | Pharmacokinetics (PK) of octreotide after injection of Sandostatin Long-acting Release (LAR) was determined for the dosing period Day -28 to Day 0; AUC0-28d (day*ng/mL). AUC0-28d: AUC from 0 to 28 days over the final dosing interval (day*ng/mL) for Sandostatin LAR. | Pre-dose; study Day -28- to Day 0 (PK analysis:Sandostatin (LAR®) sampling time points: 0, 1hour, 24hours, 7days, 14days, 21days and 28days) | 
| Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) AUC. | Pharmacokinetics (PK) of octreotide after administrations of CAM2029 was determined for the dosing period Day 0 to Day 84 ; AUC0-28d (day*ng/mL). AUC0-28d: AUC from 0 to 28 days over the dosing intervals (day*ng/mL) for CAM2029 20 mg q4w and CAM2029 10 mg q2w (to estimate AUC0-28d for those patients receiving CAM2029 10 mg q2w, AUC0-14d was multiplied by a factor of 2 as an estimate of the AUC0-28d) dosing intervals | (Day 0) to Day 84 (PK analysis:CAM2029 sampling time points: CAM2029 10mg q2w; 0, 2hours, 24hours, 48hours, 7days and 14days CAM2029 20mg q4w; 0, 2hours, 24hours, 48hours, 7days, 21days and 28days) | 
| Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Ctrough | Pharmacokinetics (PK) of octreotide after injection of Sandostatin Long-acting Release (LAR) was determined for the dosing period Day -28 to Day 0; Ctrough (ng/mL). Ctrough; Concentration levels assessed prior to next injection for the final (Sandostatin LAR) dosing interval (ng/mL). | Pre-dose; study Day -28- to Day 0 (PK analysis:Sandostatin (LAR®) sampling time points: 0, 1hour, 24hours, 7days, 14days, 21days and 28days) | 
| Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Cmax | Pharmacokinetics (PK) of octreotide after injection of Sandostatin Long-acting Release (LAR) was determined for the dosing period Day -28 to Day 0; Cmax (ng/mL). Cmax (ng/mL): Maximum observed plasma concentration over the final (Sandostatin LAR) dosing interval (ng/mL) | Pre-dose; study Day -28- to Day 0 (PK analysis:Sandostatin (LAR®) sampling time points: 0, 1hour, 24hours, 7days, 14days, 21days and 28days) | 
| Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Ctrough | Pharmacokinetics (PK) of octreotide after administrations of CAM2029 was determined for the dosing period Day 0 to Day 84; Ctrough (ng/mL). Ctrough; Concentration levels assessed prior to next injection for CAM2029 20 mg q4w and CAM2029 10 mg q2w dosing intervals (ng/mL) | (Day 0) to Day 84 (PK analysis:CAM2029 sampling time points: CAM2029 10mg q2w; 0, 2hours, 24hours, 48hours, 7days and 14days CAM2029 20mg q4w; 0, 2hours, 24hours, 48hours, 7days, 21days and 28days) | 
| Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Cmax. | Pharmacokinetics (PK) of octreotide after administrations of CAM2029 was determined for the dosing period Day 0 to Day 84 ; Cmax (ng/mL). Cmax (ng/mL): Maximum observed plasma concentration over CAM2029 20 mg q4w and CAM2029 10 mg q2w dosing intervals (ng/mL) | (Day 0) to Day 84 (PK analysis:CAM2029 sampling time points: CAM2029 10mg q2w; 0, 2hours, 24hours, 48hours, 7days and 14days CAM2029 20mg q4w; 0, 2hours, 24hours, 48hours, 7days, 21days and 28days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events and Serious Adverse Events | Safety (number of adverse events and serious adverse events) after repeated doses of CAM2029 (assessment period from Day 0 to Day 84) and single dose Sandostatin LAR (assessment period Day -28 to Day 0) | Day -28 to Day 84 | 
| CAM2029 Effect on Insulin-like Growth Factor (IGF-1) (Acromegaly) | Data is presented as number of patients Within the reference limits (see below) Above ULN (Upper Limits of Normal) In the Acromegaly group both males and females were included the age was between 42-70 years. The IGF normal range for the different genders and age are presented below. REFERENCE VALUES Males (NMOL/L) 8.34-27.44 (41-45 years) 7.7-26.36 (46-50 years) 7.3-26.34 (51-55 years) 6.64-25.44 (56-60 years) 6.17-25.02 (61-65 years) 5.96-25.48 (66-70 years) Females (NMOL/L) 8.06-26.89 (41-45 years) 7.39-25.44 (46-50 years) 6.92-24.98 (51-55 years) 5.92-22.7 (56-60 years) 5.42-21.96 (61-65 years) 5.07-21.97 (66-70 years) | Day 84 | 
| CAM2029 Effect on Growth Hormone (GH) (Acromegaly) | GH (growth hormone) levels measured on Day 84 in patients with acromegaly | Day 84 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
acromegaly, neuroendocrine tumour (NET), carcinoid syndrome, octreotide, Sandostatin LAR