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

Phase 2

Completed

• Conditions: Neuroendocrine Tumors; Acromegaly
• Interventions: Drug: octreotide FluidCrystal® injection depot

• Registration Number: NCT02299089
• Lead Sponsor: Camurus AB

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).

Study Timeline

• Study First Submitted: 2014-11-17
• Study First Submitted QC: 2014-11-21
• Study First Posted: 2014-11-24
• Study Start: 2015-01
• Primary Completion: 2016-05
• Study Completion: 2016-06
• Results First Submitted: 2017-02-01
• Status Verified: 2017-05
• Results First Submitted QC: 2017-05-16
• Last Update Submitted: 2017-05-16
• Results First Posted: 2017-12-15
• Last Update Posted: 2017-12-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CAM2029 10 mg (NET)	octreotide FluidCrystal® injection depot	CAM2029 (octreotide FluidCrystal® injection depot) 10 mg, subcutaneous injection every two weeks
CAM2029 20 mg (NET)	octreotide FluidCrystal® injection depot	CAM2029 (octreotide FluidCrystal® injection depot) 20 mg, subcutaneous injection once monthly
CAM2029 10 mg (Acromegaly)	octreotide FluidCrystal® injection depot	CAM2029 (octreotide FluidCrystal® injection depot) 10 mg, subcutaneous injection every two weeks
CAM2029 20 mg (Acromegaly)	octreotide FluidCrystal® injection depot	CAM2029 (octreotide FluidCrystal® injection depot) 20 mg, subcutaneous injection once monthly

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) AUC.	(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)	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
Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Cmax.	(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)	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)
Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Cmax	Pre-dose; study Day -28- to Day 0 (PK analysis:Sandostatin (LAR®) sampling time points: 0, 1hour, 24hours, 7days, 14days, 21days and 28days)	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)
Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) AUC	Pre-dose; study Day -28- to Day 0 (PK analysis:Sandostatin (LAR®) sampling time points: 0, 1hour, 24hours, 7days, 14days, 21days and 28days)	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.
Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Ctrough	(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)	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)

Secondary Outcome Measures

Name	Time	Method
CAM2029 Effect on Growth Hormone (GH) (Acromegaly)	Day 84	GH (growth hormone) levels measured on Day 84 in patients with acromegaly
Number of Adverse Events and Serious Adverse Events	Day -28 to Day 84	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)
CAM2029 Effect on Insulin-like Growth Factor (IGF-1) (Acromegaly)	Day 84	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)

Trial Locations

Locations (10)

CHU Rouen, Hôpital Charles Nicolle; 🇫🇷 Rouen cedex, France

Abteilung: Klinische Studien; 🇩🇪 Bad Berka, Germany

Akademiska sjukhuset; 🇸🇪 Uppsala, Sweden

Fondazione Irccs Ca' Granda; 🇮🇹 Milano, Italy

Hospices Civils de Lyon; 🇫🇷 Bron, France

Universitätsklinikum Essen; 🇩🇪 Essen, Germany

Istituto Clinico Humanitas; 🇮🇹 Rozzano, Italy

Charité Campus Virchow Klinikum; 🇩🇪 Berlin, Germany

RCCS Azienda Ospedaliera Universitaria San Martino IST; 🇮🇹 Genova, Italy

Università degli Studi di Napoli Federico II; 🇮🇹 Napoli, Italy