Clinical Trial Results:
A Phase II, Open-label, Multicentre, Randomised Study of the Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of CAM2029 in Two Patient Groups with Acromegaly and Neuroendocrine Tumours (NET) Previously Treated with Sandostatin® LAR®
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Summary
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EudraCT number |
2013-000533-12 |
Trial protocol |
DE IT |
Global end of trial date |
16 Feb 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Mar 2017
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First version publication date |
02 Mar 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
HS-12-455
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02299089 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
CAMURUS AB
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Sponsor organisation address |
Ideon Science Park, Sölvegatan 41, Sweden, SE 223 70 Lund
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Public contact |
Clinical Programme Management, Camurus AB, +46 462865730, info@camurus.com
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Scientific contact |
Clinical Programme Management, Camurus AB, +46 462865730, info@camurus.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Feb 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
16 Feb 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Feb 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study was to characterise the pharmacokinetic (PK) profile of octreotide after each injection of CAM2029 (during Period 1) as compared with baseline PK Sandostatin long acting release (LAR) (during Period 0) in patients with acromegaly and NETs.
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Protection of trial subjects |
The study was conducted according to the ethical principles of the Declaration of Helsinki. Informed consent was obtained from each patient in writing before any study-specific procedure was performed. The study was described by a nurse/study coordinator/the Investigator, who answered any questions, and written information was also provided. Final informed consent was retrieved by the physician, either investigator or co-investigator.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Jan 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 5
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Country: Number of subjects enrolled |
Germany: 4
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Country: Number of subjects enrolled |
Italy: 3
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Worldwide total number of subjects |
12
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EEA total number of subjects |
12
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
6
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From 65 to 84 years |
6
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85 years and over |
0
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Recruitment
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Recruitment details |
This study had planned to enroll 24 patients, however, only 12 patients (7 with acromegaly and 5 with neuroendocrine tumors [NETs]) were enrolled in this study. | |||||||||
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Pre-assignment
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Screening details |
Screening took place during the 14-day screening period from Day -42 to Day -29. | |||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
This was an open label trial.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Acromegaly | |||||||||
Arm description |
Twenty-eight days after the last injection of Sandostatin LAR (i.e. on Day 0), patients were randomized into the CAM2029 treatment phase (i.e. Period 1) and received their first subcutaneous thigh injection of 20 mg or 10 mg CAM2029 on Day 0. Patients randomized to receive 20 mg of CAM2029 were administered three upper thigh subcutaneous injections CAM2029 20 mg q4w on Days 0, 28 and 56; whereas patients randomized to receive 10 mg of CAM2029 were administered six upper thigh injections CAM2029 10 mg q2w on Days 0, 14, 28, 42, 56 and 70. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
CAM2029
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Investigational medicinal product code |
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Other name |
Octreotide hydrochloride FluidCrystal injection depot
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Patients were randomized to receive either 10 mg or 20 mg of CAM2029. Patients randomized to 20 mg of CAM2029 were administered three upper anterior thigh SC injections of CAM2029 20 mg q4w on Days 0, 28, and 56 and patients randomized to 10 mg of CAM2029 were administered six upper anterior thigh SC injections of CAM2029 10 mg q2w on Days 0, 14, 28, 42, 56, and 70.
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Arm title
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NETs | |||||||||
Arm description |
Twenty-eight days after the last injection of Sandostatin LAR (i.e. on Day 0), patients were randomized into the CAM2029 treatment phase (i.e. Period 1) and received their first subcutaneous thigh injection of 20 mg or 10 mg CAM2029 on Day 0. Patients randomized to receive 20 mg of CAM2029 were administered three upper thigh subcutaneous injections of CAM2029 20 mg q4w on Days 0, 28 and 56; whereas patients randomized to receive 10 mg of CAM2029 were administered six upper thigh injections CAM2029 10 mg q2w on Days 0, 14, 28, 42, 56 and 70. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
CAM2029
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Investigational medicinal product code |
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Other name |
Octreotide hydrochloride FluidCrystal injection depot
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Patients were randomized to receive either 10 mg or 20 mg of CAM2029. Patients randomized to 20 mg of CAM2029 were administered three upper anterior thigh SC injections of CAM2029 20 mg q4w on Days 0, 28, and 56 and patients randomized to 10 mg of CAM2029 were administered six upper anterior thigh SC injections of CAM2029 10 mg q2w on Days 0, 14, 28, 42, 56, and 70.
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Baseline characteristics reporting groups
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Reporting group title |
Acromegaly
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Reporting group description |
Twenty-eight days after the last injection of Sandostatin LAR (i.e. on Day 0), patients were randomized into the CAM2029 treatment phase (i.e. Period 1) and received their first subcutaneous thigh injection of 20 mg or 10 mg CAM2029 on Day 0. Patients randomized to receive 20 mg of CAM2029 were administered three upper thigh subcutaneous injections CAM2029 20 mg q4w on Days 0, 28 and 56; whereas patients randomized to receive 10 mg of CAM2029 were administered six upper thigh injections CAM2029 10 mg q2w on Days 0, 14, 28, 42, 56 and 70. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NETs
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Reporting group description |
Twenty-eight days after the last injection of Sandostatin LAR (i.e. on Day 0), patients were randomized into the CAM2029 treatment phase (i.e. Period 1) and received their first subcutaneous thigh injection of 20 mg or 10 mg CAM2029 on Day 0. Patients randomized to receive 20 mg of CAM2029 were administered three upper thigh subcutaneous injections of CAM2029 20 mg q4w on Days 0, 28 and 56; whereas patients randomized to receive 10 mg of CAM2029 were administered six upper thigh injections CAM2029 10 mg q2w on Days 0, 14, 28, 42, 56 and 70. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Acromegaly
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Reporting group description |
Twenty-eight days after the last injection of Sandostatin LAR (i.e. on Day 0), patients were randomized into the CAM2029 treatment phase (i.e. Period 1) and received their first subcutaneous thigh injection of 20 mg or 10 mg CAM2029 on Day 0. Patients randomized to receive 20 mg of CAM2029 were administered three upper thigh subcutaneous injections CAM2029 20 mg q4w on Days 0, 28 and 56; whereas patients randomized to receive 10 mg of CAM2029 were administered six upper thigh injections CAM2029 10 mg q2w on Days 0, 14, 28, 42, 56 and 70. | ||
Reporting group title |
NETs
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Reporting group description |
Twenty-eight days after the last injection of Sandostatin LAR (i.e. on Day 0), patients were randomized into the CAM2029 treatment phase (i.e. Period 1) and received their first subcutaneous thigh injection of 20 mg or 10 mg CAM2029 on Day 0. Patients randomized to receive 20 mg of CAM2029 were administered three upper thigh subcutaneous injections of CAM2029 20 mg q4w on Days 0, 28 and 56; whereas patients randomized to receive 10 mg of CAM2029 were administered six upper thigh injections CAM2029 10 mg q2w on Days 0, 14, 28, 42, 56 and 70. | ||
Subject analysis set title |
Sandostatin LAR 10 mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
This analysis group contains patients who received Sandostatin LAR 10 mg prior to the first CAM2029 injection. PK analysis set consisted of all patients who had received the study drug as scheduled.
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Subject analysis set title |
Sandostatin LAR 20 mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
This analysis group contains patients who received Sandostatin LAR 20 mg prior to the first CAM2029 injection. PK analysis set consisted of all patients who had received the study drug as scheduled.
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Subject analysis set title |
Sandostatin LAR 30 mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
This analysis group contains patients who received Sandostatin LAR 30 mg prior to the first CAM2029 injection. PK analysis set consisted of all patients who had received the study drug as scheduled.
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Subject analysis set title |
CAM2029 10 mg q2w (Acromegaly)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Randomized patients received 6 upper anterior thigh SC injections of CAM2029 10 mg q2w. PK analysis set consisted of all patients who had received the study drug as scheduled.
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Subject analysis set title |
CAM2029 10 mg q2w (NETs)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Randomized patients received 6 upper anterior thigh SC injections of CAM2029 10 mg q2w. PK analysis set consisted of all patients who had received the study drug as scheduled.
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Subject analysis set title |
CAM2029 20 mg q4w (Acromegaly)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Randomized patients received 3 upper anterior thigh SC injections of CAM2029 20 mg q4w. PK analysis set consisted of all patients who had received the study drug as scheduled.
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Subject analysis set title |
CAM2029 20 mg q4w (NETs)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Randomized patients received 3 upper anterior thigh SC injections of CAM2029 20 mg q4w. PK analysis set consisted of all patients who had received the study drug as scheduled.
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End point title |
AUC from 0 to 28 days over the final dosing intervals for Sandostatin LAR and CAM2029 study periods (AUC0-28d) in patients with acromegaly [1] | |||||||||||||||||||||||||||||||||||
End point description |
The PK endpoints included the octreotide plasma concentration curve versus time and PK parameters for Sandostatin LAR and CAM2029 in patients with acromegaly. Serial blood samples were collected from Day -28 to Day 84.
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End point type |
Primary
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End point timeframe |
Sandostatin LAR 10 mg and 30 mg on Day -28 (Period 0) and CAM2029 10 mg q2w and 20 mg q4w on Day 0 and Day 56 (Period 1).
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analysis was done. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||
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End point title |
AUC from 0 to 28 days over the final dosing intervals for Sandostatin LAR and CAM2029 study periods (AUC0-28d) in patients with NETs [2] | |||||||||||||||||||||||||||||||||||
End point description |
The PK endpoints included the octreotide plasma concentration curve versus time and PK parameters for Sandostatin LAR and CAM2029 in patients with NETs. Serial blood samples were collected from Day -28 to Day 84.
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End point type |
Primary
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End point timeframe |
Sandostatin LAR 20 mg and 30 mg on Day -28 (Period 0) and CAM2029 10 mg q2w and 20 mg q4w on Day 0 and Day 56 (Period 1).
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analysis was done. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||
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End point title |
Concentration levels assessed prior to next injection for the final (Sandostatin LAR, CAM2029 q4w) or penultimate (CAM2029 q2w only) dosing interval (Ctrough) in patients with acromegaly [3] | |||||||||||||||||||||||||||||||||||
End point description |
The PK endpoints included the octreotide plasma concentration curve versus time and PK parameters for Sandostatin LAR and CAM2029 in patients with acromegaly. Serial bood samples were collected from Day -28 to Day 84.
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End point type |
Primary
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End point timeframe |
Sandostatin LAR 10 mg and 30 mg on Day -28 (Period 0) and CAM2029 10 mg q2w and 20 mg q4w on Day 0 and Day 56 (Period 1).
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analysis was done. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||
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End point title |
Concentration levels assessed prior to next injection for the final (Sandostatin LAR, CAM2029 q4w) or penultimate (CAM2029 q2w only) dosing interval (Ctrough) in patients with NETs [4] | |||||||||||||||||||||||||||||||||||
End point description |
The PK endpoints included the octreotide plasma concentration curve versus time and PK parameters for Sandostatin LAR and CAM2029 in patients with NETs. Serial blood samples were collected from Day -28 to Day 84.
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End point type |
Primary
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End point timeframe |
Sandostatin LAR 20 mg and 30 mg on Day -28 (Period 0) and CAM2029 10 mg q2w and 20 mg q4w on Day 0 and Day 56 (Period 1).
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analysis was done. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||
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End point title |
Maximum observed plasma concentration over the final (Sandostatin LAR, CAM2029 q4w) or penultimate (CAM2029 q2w only) dosing interval (Cmax) for patients with acromegaly [5] | |||||||||||||||||||||||||||||||||||
End point description |
The PK endpoints included the octreotide plasma concentration curve versus time and PK parameters for Sandostatin LAR and CAM2029 in patients with acromegaly. Serial blood samples were collected from Day -28 to Day 84.
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End point type |
Primary
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End point timeframe |
Sandostatin LAR 10 mg and 30 mg on Day -28 (Period 0) and CAM2029 10 mg q2w and 20 mg q4w on Day 0 and Day 56 (Period 1).
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analysis was done. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||
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End point title |
Maximum observed plasma concentration over the final (Sandostatin LAR, CAM2029 q4w) or penultimate (CAM2029 q2w only) dosing interval (Cmax) for patients with NETs [6] | |||||||||||||||||||||||||||||||||||
End point description |
The PK endpoints included the octreotide plasma concentration curve versus time and PK parameters for Sandostatin LAR and CAM2029 in patients with NETs. Serial blood samples were collected from Day -28 to Day 84.
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End point type |
Primary
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End point timeframe |
Sandostatin LAR 20 mg and 30 mg on Day -28 (Period 0) and CAM2029 10 mg q2w and 20 mg q4w on Day 0 and Day 56 (Period 1).
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistical analysis was done. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||
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End point title |
Proportion of patients with acromegaly whose Insulin-like growth factor-1 (IGF-1) levels are above and within normal limits on Day 84 | |||||||||||||||
End point description |
The proportion of patients with IGF-1 levels within or above normal on Day 84 were summarized by treatment.
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End point type |
Secondary
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End point timeframe |
Day 84 (Period 1).
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Proportion of patients with acromegaly with growth hormone (GH) levels <2.5 μg/L on Day 84 | ||||||||||||
End point description |
The proportion of patients with normalization of GH (adjusted for age and gender) <2.5 µg/L, at baseline and on Day 84 were summarized by treatments.
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End point type |
Secondary
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End point timeframe |
Day 84 (Period 1).
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events (AEs) were collected from the date of signing of informed consent to the final follow up visit.
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Adverse event reporting additional description |
In case of early termination (before Day 84), the patients were monitored for safety for 28 days after the last CAM2029 treatment cycle and underwent assessments and procedures at the end of the Post-treatment Phase (Day 111).
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Acromegaly
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Reporting group description |
Twenty-eight days after the last injection of Sandostatin LAR (i.e. on Day 0), patients were randomized into the CAM2029 treatment phase (i.e. Period 1) and received their first subcutaneous thigh injection of 20 mg or 10 mg CAM2029 on Day 0. Patients randomized to receive 20 mg of CAM2029 were administered three upper thigh subcutaneous injections CAM2029 20 mg q4w on Days 0, 28 and 56; whereas patients randomized to receive 10 mg of CAM2029 were administered six upper thigh injections CAM2029 10 mg q2w on Days 0, 14, 28, 42, 56 and 70. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NETs
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Reporting group description |
Twenty-eight days after the last injection of Sandostatin LAR (i.e. on Day 0), patients were randomized into the CAM2029 treatment phase (i.e. Period 1) and received their first subcutaneous thigh injection of 20 mg or 10 mg CAM2029 on Day 0. Patients randomized to receive 20 mg of CAM2029 were administered three upper thigh subcutaneous injections of CAM2029 20 mg q4w on Days 0, 28 and 56; whereas patients randomized to receive 10 mg of CAM2029 were administered six upper thigh injections CAM2029 10 mg q2w on Days 0, 14, 28, 42, 56 and 70. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Jun 2014 |
Amendment 1 was implemented based on request from Swedish Health Authority primarily:
1. Updated the name of the Medical Monitor.
2. Clarified the exclusion criteria for each patient population to exclude patients with angina or a history of myocardial infarction within 6 months prior to starting treatment.
3. Clarified that patients were to restart their pre-study regimen with Sandostatin LAR on Day 84 (Period 2).
4. Clarified the Schedule of Events Table that safety laboratory test samples would only be taken on dosing days for each patient population. |
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25 Jul 2014 |
Amendment 2 was implemented based on request from the French Independent Ethics Committee:
1. Added assessments for pre-dose fasting plasma glucose on all days when PK sampling was performed and provided instruction for the management of elevated fasting plasma glucose.
2. Added procedures and specifications to manage hepatic safety by monitoring clinical laboratory values.
3. Added an HbA1c test to occur on Day 56. |
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29 Aug 2014 |
Amendment 3 primarily implemented the following modifications:
1. Specified urgent safety measures as the trigger for early termination on a study level.
2. Added patient discontinuation criteria. |
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23 Sep 2014 |
Amendment 4 was a substantial global amendment to implement the following modifications, including country-specific (previous) amendments:
1. Authorized the use of Longastatina LAR for patients in Italy. Longastatina LAR is the same drug as Sandostatin LAR and is manufactured by the same company, but is commercialized as Longastatina LAR in Italy.
2. Updated the name of the Medical Monitor.
3. Changed the injection site from buttock to upper thigh.
4. Specified urgent safety measures as the trigger for early termination on a study level.
5. Clarified the exclusion criteria for each patient population to exclude patients with angina or a history of myocardial infarction within 6 months prior to screening.
6. Updated exclusion criteria regarding previous surgeries to include the 2-month period before screening rather than randomization.
7. Updated exclusion criteria regarding previous alcohol abuse to include the 12-month period before screening rather than randomization.
8. Added exclusion criteria regarding prior medications.
9. Clarified that patients would restart their pre-study regimen with Sandostatin LAR on Day 84 (Period 2).
10. Added patient discontinuation criteria based on safety criteria.
11. Added procedures and specifications to manage hepatic safety by monitoring clinical laboratory values.
12. Added an HbA1c test to occur on Day 56.
13. Added assessments for pre-dose fasting plasma glucose on all days when PK sampling performed and provided instruction for the management of elevated fasting plasma glucose.
14. Allowed historical abdominal ultrasound of the gallbladder for study use, if was performed within 2 months prior to screening.
15. Clarified the Schedule of Events Tables that safety laboratory test samples would only be taken on dosing days for each patient population. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
