Study to Determine the Maximum Tolerated Dose, Safety and Tolerability of a Single Dose of Lanreotide Prolonged Release Formulation (PRF) in Subjects With Acromegaly

NCT02396953 | Completed Phase 1 Results DMC

• 2 other identifiers: 8-55-52030-3092014-002389-62
• Study Type: interventional
• Target: 28
• Locations: 12 countries
• Sites: 36

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.

Conditions

Acromegaly

Outcome Measures

Primary Outcomes (6)

• Determination of the Maximum Tolerated Dose (MTD) by Number of Subjects With DLTs.

  The MTD was defined based on the DLTs observed in each cohort. A DLT was defined as an adverse event (AE) (excluding anorexia and fatigue) or an abnormal laboratory value occurring within the first week (up to Week 2) following lanreotide PRF administration and during the entire study duration, assessed as unrelated to acromegaly, intercurrent illness or concomitant medications and which met any of the pre-established toxicity criteria. If no DLTs were reported then no MTD could be defined.

  From Day 1 up to Week 25.

• PK Analysis of Lanreotide: Maximum Observed Serum Concentration (Cmax).

  Blood samples for determination of lanreotide serum concentrations were collected at Baseline (pre-dose), at 1, 2, 4, 6, 8,12 and 24 hours post-dose, on Days 3 and 5 and at Weeks 2, 3, 5, 9 and 13 after lanreotide PRF administration. Samples were also collected during follow-up at Weeks 17, 21 and 25 (or EW). Mean serum lanreotide Cmax values were determined using non-compartmental analysis.

  From Baseline (pre-dose) up to Week 25.

• PK Analysis of Lanreotide: Time to Reach Maximum Serum Concentration (Tmax).

  Blood samples for determination of lanreotide serum concentrations were collected at Baseline (pre-dose), at 1, 2, 4, 6, 8,12 and 24 hours post-dose, on Days 3 and 5 and at Weeks 2, 3, 5, 9 and 13 after lanreotide PRF administration. Samples were also collected during follow-up at Weeks 17, 21 and 25 (or EW). Median serum lanreotide Tmax values were determined using non-compartmental analysis.

  From Baseline (pre-dose) up to Week 25.

• PK Analysis of Lanreotide: Apparent Terminal Elimination Half-life (t1/2).

  Blood samples for determination of lanreotide serum concentrations were collected at Baseline (pre-dose), at 1, 2, 4, 6, 8,12 and 24 hours post-dose, on Days 3 and 5 and at Weeks 2, 3, 5, 9 and 13 after lanreotide PRF administration. Samples were also collected during follow-up at Weeks 17, 21 and 25 (or EW). Mean serum lanreotide t1/2 values were determined using non-compartmental analysis. Only values fulfilling the determination rules for t1/2 were analysed.

  From Baseline (pre-dose) up to Week 25.

• PK Analysis of Lanreotide: Area Under the Serum Concentration-time Curve From Time 0 to 85 Days (AUC0-85).

  Blood samples for determination of lanreotide serum concentrations were collected at Baseline (pre-dose), at 1, 2, 4, 6, 8,12 and 24 hours post-dose, on Days 3 and 5 and at Weeks 2, 3, 5, 9 and 13 after lanreotide PRF administration. Sample were also collected during follow-up at Weeks 17, 21 and 25 (or EW). Mean serum lanreotide AUC0-85 values were determined using non-compartmental analysis.

  From Baseline (pre-dose) up to Day 85

• PK Analysis of Lanreotide: Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUC0-∞).

  Blood samples for determination of lanreotide serum concentrations were collected at Baseline (pre-dose), at 1, 2, 4, 6, 8,12 and 24 hours post-dose, on Days 3 and 5 and at Weeks 2, 3, 5, 9 and 13 after lanreotide PRF administration. Samples were also collected during follow-up at Weeks 17, 21 and 25 (or EW). Mean serum lanreotide AUC0-∞ values were determined using non-compartmental analysis. Only values fulfilling the accuracy determination rules for AUC0-∞ were analysed.

  From Baseline (pre-dose) up to Week 25.

Secondary Outcomes (9)

• Overall Summary of Number of Subjects With AEs.

  From Day -42 up to Week 25.

• PK Analysis of Glycofurol Excipients: Cmax.

  From Baseline (pre-dose) up to Day 5.

• PK Analysis of Glycofurol Excipients: Tmax.

  From Baseline (pre-dose) up to Day 5.

• PK Analysis of Glycofurol Excipients: AUC0-∞ and Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Timepoint (AUC0-t).

  From Baseline (pre-dose) up to Day 5.

• PD Analysis: Mean Change From Baseline in Insulin-like Growth Factor 1 (IGF-1).

  From Baseline (pre-dose) up to Week 25.

Study Arms (1)

lanreotide PRF

EXPERIMENTAL

One single dose of lanreotide PRF (via subcutaneous injection) either 180mg or 270mg or 360mg.

Drug: Lanreotide PRF

Interventions

Lanreotide PRF DRUG

Also known as: Lanreotide acetate

lanreotide PRF

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ipsen: lead

Study Sites (36)

Antwerp University Hospital

Edegem, Belgium

Location

Domaine Universitaire Sart Tilman

Liège, Belgium

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, Czechia

Location

Fakultní nemocnice Hradec Králové (University Hospital Hradec)

Hradec Králové, Czechia

Location

CHU le BOCAGE

Dijon, 21079, France

Location

Hôpital de Bicêtre (AP-HP)

Le Kremlin-Bicêtre, 94275, France

Location

CHU de la Timone

Marseille, 13385, France

Location

Hôpital Haut Lévêque

Pessac, 33604, France

Location

University Medicine Berlin

Berlin, 10117, Germany

Location

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

IRCCS AOU San Martino-IST, University of Genova

Genova, 16139, Italy

Location

Azienda Ospedaliera Padova

Padua, 35128, Italy

Location

Policlinico of Palermo

Palermo, 90127, Italy

Location

Ospedale Cisanello

Pisa, 56124, Italy

Location

Azienda Ospedaliera Universitaria Senese

Siena, 53100, Italy

Location

AO Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Lithuanian University of Health Sciences (LUHS) Kauno klinikos

Kaunas, Lithuania

Location

Vilnius University hospital Santariskiu Klinikos

Vilnius, Lithuania

Location

Erasmus University Medical Centre Rotterdam

Rotterdam, 3000 ca, Netherlands

Location

Uniwersytecki Szpital Kliniczny w Białymstoku

Bialystok, 15-276, Poland

Location

Szpital Kliniczny im. H. Święcickiego UM w Poznaniu

Poznan, 60-355, Poland

Location

Szpital Bielanski im. ks. Jerzego Popieluszki SPZOZ

Warsaw, 01-809, Poland

Location

Szpital Kliniczny nr 1

Wroclaw, 50-367, Poland

Location

National Institute of Endocrinology

Bucharest, 11863, Romania

Location

Kazan state Medical Academy

Kazan', 420012, Russia

Location

Kemerovo Regional Clinical Hospital

Kemerovo, 650066, Russia

Location

Endocrinological Research Center Ministry of Health Russian Federation

Moscow, 117036, Russia

Location

Healthcare Institution

Nizhny Novgorod, 603126, Russia

Location

Federal State Budgetary Military

Saint Petersburg, 191015, Russia

Location

North-Western State Medical University

Saint Petersburg, 191015, Russia

Location

Hospital Universitario Vall d' Hebron

Barcelona, 08035, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Queen Mary, University of London

London, EC1M 6BQ, United Kingdom

Location

Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34664531 DERIVED

MeSH Terms

Conditions

Acromegaly

Interventions

lanreotide

Condition Hierarchy (Ancestors)

Bone Diseases, Endocrine; Bone Diseases; Musculoskeletal Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Limitations and Caveats

No glycofurol excipient PK results are available for 360mg Lanreotide PRF at this time. A total of 28 subjects were allowed to enrol rather than the 27 subjects planned as it was considered unethical not to enrol a consented eligible subject.

Results Point of Contact

• Title: Medical Director
• Organization: Ipsen

clinical.trials@ipsen.com

Use email address below

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2015
• First Posted: March 24, 2015
• Study Start: March 1, 2015
• Primary Completion: November 28, 2017
• Study Completion: November 28, 2017
• Last Updated: April 25, 2019
• Results First Posted: April 25, 2019

Record last verified: 2019-04

Locations

IT (6); RO (1); GB (3); CZ (2); DE (2); BE (2); RU (6); LI (2); FR (4); NL (1); PL (4); ES (3)