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

Neuroendocrine Tumors Clinical Trial

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®

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02299089
• Other study ID #: HS-12-455
• Status: Completed
• Phase: Phase 2
• First received: November 17, 2014
• Last updated: May 16, 2017
• Start date: January 2015
• Est. completion date: June 2016

Study information

• Verified date: May 2017
• Source: Camurus AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: June 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acromegaly
• Carcinoid Tumor
• Neuroendocrine Tumors

Intervention

Drug:
• octreotide FluidCrystal® injection depot

Locations

Country	Name	City	State
France	Hospices Civils de Lyon	Bron
France	CHU Rouen, Hôpital Charles Nicolle	Rouen cedex
Germany	Abteilung: Klinische Studien	Bad Berka
Germany	Charité Campus Virchow Klinikum	Berlin
Germany	Universitätsklinikum Essen	Essen
Italy	RCCS Azienda Ospedaliera Universitaria San Martino IST	Genova
Italy	Fondazione Irccs Ca' Granda	Milano
Italy	Università degli Studi di Napoli Federico II	Napoli
Italy	Istituto Clinico Humanitas	Rozzano
Sweden	Akademiska sjukhuset	Uppsala

Sponsors (2)

Lead Sponsor	Collaborator
Camurus AB	Novartis

Countries where clinical trial is conducted

France,  Germany,  Italy,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To Assess the Symptoms of Carcinoid Syndrome (Number of Bowel Movements and Flushing) and the Use of Rescue Medication Versus Baseline (by Using Patient Diaries) (NET)	Number of bowel movements and flushing during period 0 and 1, data is presented as patients experience symptoms; Bowel movement without flushing Bowel movement and flushing No Bowel movement or Flushing	Baseline (Day 0), Day 84
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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
Secondary	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
Secondary	CAM2029 Effect on Growth Hormone (GH) (Acromegaly)	GH (growth hormone) levels measured on Day 84 in patients with acromegaly	Day 84