Acromegaly MedDRA version: 19.1 Level: PT Classification code 10000599 Term: Acromegaly System Organ Class: 10014698 - Endocrine disorders
Conditions
Interventions
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 na
Sponsors
Ipsen Group
Eligibility
Sex/Gender
All
Inclusion 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 ocreotide 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 =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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;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 ;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 adminis | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Belgium, Czech Republic, France, Germany, Italy, Lithuania, Netherlands, Poland, Romania, Russian Federation, Spain, United Kingdom
Contacts
Public ContactExecutive VP Research & Development
Ipsen Group
Outcome results
None listed