A clinical trial to determine the maximum dose, safety and tolerability of one injection of lanreotide prolonged release formulation in patients with acromegaly previously treated with either octreotide LAR or lanreotide Autogel

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2014-002389-62-GB
• Date of registration: 02/10/2014
• Prospective Registration: Yes
• Primary sponsor: Ipsen Group
• Public title: A clinical trial to determine the maximum dose, safety and tolerability of one injection of lanreotide prolonged release formulation in patients with acromegaly previously treated with either octreotide LAR or lanreotide Autogel
• Scientific title: Phase IIa, open label, dose ascending study to determine the maximum tolerated dose, safety and tolerability, pharmacokinetics and pharmacodynamics of a single dose of lanreotide PRF in subjects with acromegaly previously treated and controlled with either octreotide LAR or lanreotide Autogel
• Date of first enrolment: 02/03/2015
• Target sample size: 27
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002389-62
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, France, Germany, Hungary, Italy, Lithuania, Netherlands, Poland, Romania, Russian Federation, Spain, United Kingdom

Contacts

• Name: Executive VP Research & Development
• Affiliation: Ipsen Group

• Name: Executive VP Research & Development
• Affiliation: Ipsen Group

Key inclusion & exclusion criteria

Inclusion criteria:
All subjects must fulfil all of the following criteria to be included in the study:
- Documented diagnosis of acromegaly.
- Provided written informed consent prior to any study related procedures.
- Between 18 and 75 years of age inclusive.
- Female of nonchildbearing potential or male. Nonchildbearing potential is defined as being postmenopausal for at least 1 year, or women with documented infertility (natural or acquired).
- Male subjects must agree that, if their partner is at risk of becoming pregnant, they will use a medically accepted, effective method of contraception (i.e. condom) for the duration of the study (up to 7.5 months).
- Treatment with a stable dose of either octreotide LAR or lanreotide Autogel for at least 3 months immediately prior to study entry, with confirmation of disease control during this treatment period (documentation of age adjusted IGF-1 <1.3 x ULN, based on local laboratory results, during the Screening period.
- If the subject is receiving treatment for hypertension, the dose has been stable for at least 1 month prior to study entry.
- Subjects must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period and willing to return to the clinic for the follow up evaluation as specified in the protocol.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion criteria:
Subjects will not be included in the study if the subject:
- Has undergone radiotherapy within 2 years prior to study entry.
- Has been treated with a dopamine agonist and/or GH receptor
antagonist or has undergone pituitary surgery within 3 months prior to study entry.
- Is anticipated to require pituitary surgery or radiotherapy during the
study.
- Has clinically significant hepatic abnormalities and/or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =3 x ULN and/or alkaline phosphatase (AP) =2.5 x ULN and/or total bilirubin =1.5 x ULN and/or gamma-glutamyl transpeptidase (GGT) =2.5 x ULN during the Screening period (central laboratory results) or a history of these findings when on somatostatin analogue (SSTa) treatment.
- Has clinically significant pancreatic abnormalities and/or amylase
and/or lipase =1.5 x ULN during the Screening period (central laboratory results).
- Has any significant renal abnormalities and/or creatinine =1.5 x ULN during the Screening period (central laboratory results).
- Has uncontrolled diabetes (glycosylated haemoglobin (HbA1c) =9%, centrally assessed during the Screening period), or has diabetes treated with insulin for less than 6 months prior to study entry.
- Has any known uncontrolled cardiovascular disease or had any of the following within 6 months of Screening: ventricular or atrial dysrhythmia =grade 2, bradycardia =grade 2, electrocardiogram (ECG) QT interval corrected (QTc) prolonged =grade 2, myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, hypertension not adequately controlled by current medications.
- Use of any hormone replacement therapy (HRT) with oestrogens.
- Has symptomatic gallstones/sludge at the Screening Visit echography (local assessment) OR is asymptomatic but has echography showing clear evidence of impending inflammation such as localised mucosal thickening suggesting the subject is at high risk of developing acute
disease. Subjects with asymptomatic gallstones/sludge and otherwise normal echography may be entered at the discretion of the investigator.
- Has abnormal findings during the Screening period, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardise the subject's safety.
- Has been treated with any other investigational medicinal product (IMP) prior to the first study visit without undergoing a washout period of seven times the elimination half life of the investigational compound.
- Has a known hypersensitivity to any of the test materials or related compounds.
- Is likely to require treatment during the study with drugs that are not permitted by the study protocol.
- Has a history of, or known current, problems with alcohol or drug abuse.
- Has any mental condition rendering him/her unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Acromegaly
MedDRA version: 19.0 Level: PT Classification code 10000599 Term: Acromegaly System Organ Class: 10014698 - Endocrine disorders

Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Intervention(s)

Product Name: Lanreotide PRF
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Lanreotide acetate
CAS Number: 127984-74-1
Current Sponsor code: BN 52030, BIM-23014C
Other descriptive name: LANREOTIDE ACETATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 180-

Product Name: Lanreotide PRF
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Lanreotide acetate
CAS Number: 127984-74-1
Current Sponsor code: BN 52030, BIM-23014C
Other descriptive name: LANREOTIDE ACETATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 270-

Product Name: Lanreotide PRF
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Lanreotide acetate
CAS Number: 127984-74-1
Current Sponsor code: BN 52030, BIM-23014C
Other descriptive name: LANREOTIDE ACETATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 360-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: •Safety Variables - Timepoints depend on the type of variable

•Lanreotide serum concentration
Baseline (predose on Day 1 of lanreotide PRF administration)
-At 1, 2, 4, 6, 8 and 12 hours postdose on the day of dosing (Day 1)
-At 24 hours postdose (Day 2)
-On Days 3 and 5, and at Weeks 2, 3, 5, 9 and 13 after lanreotide PRF administration (the Week 13 sample will be on Day 85 and will correspond to the concentration at the end of the dosing interval (Ctrough))
-At Weeks 17, 21 and 25 (or EW) during follow up

•Excipient serum concentration
-Baseline (predose on Day 1 of lanreotide PRF administration)
-At 1, 2, 4, 6, 8 and 12 hours postdose on the day of dosing (Day 1), at 24 hours postdose (Day 2), and on Days 3 and 5 after lanreotide PRF administration

Secondary Objective: •To investigate the safety and tolerability of a single dose of lanreotide PRF
•To investigate the pharmacodynamics (PD) of a single dose of lanreotide PRF
•To investigate the PK of the excipient

Main Objective: To identify the maximum tolerated dose (MTD) and to investigate the pharmacokinetics (PK) of a single dose of lanreotide PRF in subjects with acromegaly

Primary end point(s): Safety variables
•Adverse events
•Vital signs (supine and standing blood pressure, heart rate, body temperature)
•Physical examination
•12 lead electrocardiogram (ECG), QT interval corrected (QTc) will be calculated using Fridericia methodology
•Clinical laboratory assessments: haematology, coagulation, clinical biochemistry, urinalysis
•Glycosylated haemoglobin (HbA1c)
•Estimated glomerular filtration rate (eGFR) estimated by the Modification of Diet in Renal Disease (MDRD) formula
•Gallbladder echography
•Putative antibodies to lanreotide
•Evaluation of injection site reactions (appearance, local symptoms)

Pharmacokinetic variables:
•Lanreotide serum concentration

•Lanreotide PK parameters
-Ctrough
-maximum serum concentration (Cmax)
-Tmax
-area under the serum concentration time curve from time 0 to 85 days (AUC 0-85)
-area under the concentration time curve extrapolated to infinity (AUC 0-inf)
-t½
-mean residence time (MRT)
-apparent clearance (CL/F)
-apparent volume of distribution (V/F)

•Excipient serum concentration

•Excipient PK parameters
-Cmax
-Tmax
-area under the serum concentration time curve from time 0 to last quantifiable timepoint (AUCt)
-AUC 0-inf
-t½
-MRT
-CL/F
-V/F

Secondary Outcome(s)

Secondary end point(s): Pharmacodynamics variables
•IGF 1
•GH cycle (five sampling times with a sample every 30 minutes for 2 hours in the morning)
•Random GH sample
•Free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH) and prolactin (PRL)

Timepoint(s) of evaluation of this end point: IGF-1: screening, baseline (pre-dose), 6 hrs post-dose on Day 1, Wks 5, 9, 13 and Wks 17, 21 and 25/EW during follow up
GH cycle: screening, baseline (pre-dose), Wks 5 and 13
Random GH sample: 6 hrs post dose on Day 1, Wk 9, and Wks 17, 21 and 25/EW during follow up
FT3/FT4/TSH/PRL: screening, baseline (pre-dose), Wks 2, 5 and 13, and Wk 25/EW during follow up

Secondary ID(s)

8-55-52030-309

Source(s) of Monetary Support

Ipsen Group

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 09/11/2018
• Date Completed: 28/11/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002389-62/results