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 ocreotide LAR

• Register: EUCTR
• Last refreshed on: 19 February 2018
• Main ID: EUCTR2014-002389-62-IT
• Date of registration: 10/03/2016
• Prospective Registration: No
• Primary sponsor: IPSEN PHARMA SAS
• 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 ocreotide LAR
• Scientific title: Phase IIA, open label, dose ascending study to determine the maximum tolerated dose, safety and tolerability, pharmacokinetics and parmacodynamics of a single dose of lanreotide PRF in subjects with acromegaly previously treated and controlled with ocreotide LAR
• Date of first enrolment: 07/04/2015
• 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
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes 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 non childbearing potential or male. Non childbearing 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 (maximum of 7 months).
- Treatment with a stable dose of octreotide LAR 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 - 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 3 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.
- 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 a history of gallstones or any gallstones/sludge observed at Screening gallbladder echography (local assessment).
- 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: 18.1 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 ACETATO
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 ACETATO
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: Suspension for injection
INN or Proposed INN: LANREOTIDE ACETATO
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)

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

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

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

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 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

2014-002389-62-GB

Source(s) of Monetary Support

Azienda Farmaceutica: Ipsen Group