Clinical trial NCT02396953: Study to Determine the Maximum Tolerated Dose, Safety and Tolerability of a Single Dose of Lanreotide Prolonged Release Formulation (PRF) in Subjects With Acromegaly
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acromegaly
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2015-03-24
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objectives of the protocol is to determine the maximum tolerated dose and to investigate the pharmacokinetics of a single dose of lanreotide PRF in subjects with acromegaly.


Eligibility criteria: Inclusion Criteria:

* 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 7.5 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 upper limit of normal (ULN), based on local laboratory results, during 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Determination of the Maximum Tolerated Dose (MTD) by Number of Subjects With DLTs.
timeFrame: From Day 1 up to Week 25.
measure: PK Analysis of Lanreotide: Maximum Observed Serum Concentration (Cmax).
timeFrame: From Baseline (pre-dose) up to Week 25.
measure: PK Analysis of Lanreotide: Time to Reach Maximum Serum Concentration (Tmax).
timeFrame: From Baseline (pre-dose) up to Week 25.
measure: PK Analysis of Lanreotide: Apparent Terminal Elimination Half-life (t1/2).
timeFrame: From Baseline (pre-dose) up to Week 25.
measure: PK Analysis of Lanreotide: Area Under the Serum Concentration-time Curve From Time 0 to 85 Days (AUC0-85).
timeFrame: From Baseline (pre-dose) up to Day 85
measure: PK Analysis of Lanreotide: Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUC0-∞).
timeFrame: From Baseline (pre-dose) up to Week 25.
Secondary outcomes:
measure: Overall Summary of Number of Subjects With AEs.
timeFrame: From Day -42 up to Week 25.
measure: PK Analysis of Glycofurol Excipients: Cmax.
timeFrame: From Baseline (pre-dose) up to Day 5.
measure: PK Analysis of Glycofurol Excipients: Tmax.
timeFrame: From Baseline (pre-dose) up to Day 5.
measure: PK Analysis of Glycofurol Excipients: AUC0-∞ and Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Timepoint (AUC0-t).
timeFrame: From Baseline (pre-dose) up to Day 5.
measure: PD Analysis: Mean Change From Baseline in Insulin-like Growth Factor 1 (IGF-1).
timeFrame: From Baseline (pre-dose) up to Week 25.
measure: PD Analysis: Mean Change From Baseline in Growth Hormone (GH).
timeFrame: From Baseline (pre-dose) up to Week 13.
measure: PD Analysis: Mean Change From Baseline in Free Triiodothyroxine (FT3) and Free Thyroxine (FT4).
timeFrame: From Baseline (pre-dose) up to Week 25.
measure: PD Analysis: Mean Change From Baseline in Thyroid Stimulating Hormone (TSH).
timeFrame: From Baseline (pre-dose) up to Week 25.
measure: PD Analysis: Mean Change From Baseline in Prolactin.
timeFrame: From Baseline (pre-dose) up to Week 25.
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Liège
country: Belgium
facility: Domaine Universitaire Sart Tilman
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Hradec Králové
country: Czechia
facility: Fakultní nemocnice Hradec Králové (University Hospital Hradec)
city: Dijon
country: France
facility: CHU le BOCAGE
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital de Bicêtre (AP-HP)
city: Marseille
country: France
facility: CHU de la Timone
city: Pessac
country: France
facility: Hôpital Haut Lévêque
city: Berlin
country: Germany
facility: University Medicine Berlin
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Genova
country: Italy
facility: IRCCS AOU San Martino-IST, University of Genova
city: Padova
country: Italy
facility: Azienda Ospedaliera Padova
city: Palermo
country: Italy
facility: Policlinico of Palermo
city: Pisa
country: Italy
facility: Ospedale Cisanello
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese
city: Torino
country: Italy
facility: AO Città della Salute e della Scienza di Torino
city: Kaunas
country: Lithuania
facility: Lithuanian University of Health Sciences (LUHS) Kauno klinikos
city: Vilnius
country: Lithuania
facility: Vilnius University hospital Santariskiu Klinikos
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Centre Rotterdam
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Białymstoku
city: Poznan
country: Poland
facility: Szpital Kliniczny im. H. Święcickiego UM w Poznaniu
city: Warszawa
country: Poland
facility: Szpital Bielanski im. ks. Jerzego Popieluszki SPZOZ
city: Wroclaw
country: Poland
facility: Szpital Kliniczny nr 1
city: Bucharest
country: Romania
facility: National Institute of Endocrinology
city: Kazan
country: Russian Federation
facility: Kazan state Medical Academy
city: Kemerovo
country: Russian Federation
facility: Kemerovo Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: Endocrinological Research Center Ministry of Health Russian Federation
city: Nizhniy Novgorod
country: Russian Federation
facility: Healthcare Institution
city: Saint-Petersburg
country: Russian Federation
facility: Federal State Budgetary Military
city: Saint-Petersburg
country: Russian Federation
facility: North-Western State Medical University
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d' Hebron
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: London
country: United Kingdom
facility: Queen Mary, University of London
city: Manchester
country: United Kingdom
facility: Christie NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References:
citation: Neggers S, Badiu C, Biagetti B, Durand-Gasselin L, Petit A, Petrossians P, Regnault B, Rich D, Shafigullina Z, Shustov S, Vydrych A. Pharmacological and safety profile of a prolonged-release lanreotide formulation in acromegaly. Expert Rev Clin Pharmacol. 2021 Dec;14(12):1551-1560. doi: 10.1080/17512433.2021.1986004. Epub 2021 Nov 8.