Clinical research in patients with acromegaly for the assessment of test product BIM23B065, that will be given to them as repeated subcutaneous injectio

Phase 1

Conditions: MedDRA version: 19.1Level: PTClassification code 10000599Term: AcromegalySystem Organ Class: 10014698 - Endocrine disorders
Therapeutic area: Diseases [C] - Hormonal diseases [C19]
Confirmed diagnosis of acromegaly, with or without a history of pituitary surgery, treatment naïve patients or patients that have received prior treatment for their acromegaly.
MedDRA version: 19.1Level: PTClassification code 10052389Term: Pre-surgical treatment of acromegalySystem Organ Class: 10042613 - Surgical and medical procedures

Registration Number: EUCTR2015-003868-37-BG

Lead Sponsor: Ipsen Pharma SAS

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 24

Inclusion Criteria

(1) Provided written informed consent prior to any study related procedures.
(2) Subjects will have a documented diagnosis of acromegaly.
(3) Subjects will have active acromegaly confirmed by a mean serum concentration of GH over 2 hours > 2.5 µg/L at screening analysed by central laboratory.
(4) Subjects who have had pituitary surgery must be >8 weeks post-surgery.
(5) 18 to 75 years of age.
(6) Negative pregnancy test (female subjects).
(7) Female who is either of non-childbearing potential or who is not pregnant at screening and agrees to use highly effective contraception during whole duration of the study. Non-childbearing potential is defined as being postmenopausal for at least 1 year, or women with documented infertility (natural or acquired).
(8) 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 treatment period of the study.
(9) 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 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion Criteria

(1) The subject has received long-acting SSA within 12 weeks prior screening (e.g. octreotide long acting release (LAR), lanreotide Autogel, pasireotide LAR).
(2) The subject has received short-acting SSA within 1 week (e.g. octreotide s.c.) prior to screening.
(3) The subject has received a dopamine agonist within 6 weeks (e.g. bromocriptine or cabergoline) prior to screening.
(4) The subject has received GH antagonist within 12 weeks prior to screening (e.g. pegvisomant).
(5) The subject had undergone radiotherapy to the pituitary gland at any time prior to study entry.
(6) It is anticipated that the subject will undergo pituitary surgery or radiation to the pituitary gland during the study, or will require additional medical therapy for acromegaly (including SSA, pegvisomant, or dopamine agonists) during the study.
(7) The subject has unsubstituted/untreated adrenal insufficiency.
(8) If the subject has any history of postural hypotension or evidence of
postural hypotension at screening (>= 20 mm Hg decrease in SBP, >= 10 mm Hg
decrease in DBP, or >=30 bpm increases in pulse rate, after standing for 2 minutes from resting supine position of at least 10 min).
(9) Subject with poorly controlled diabetes mellitus (presence of ketoacidosis or a glycosylated haemoglobin level >10%).
(10) Subject with diabetes treated with insulin for less than 6 weeks prior to study entry, or with an unstable insulin dose in the 6 weeks prior to study entry or Haemoglobin A1c (HbA1c) >10%.
(11) Subject is taking beta-blockers (which can inhibit compensatory
increases in HR during hypotensive episodes).
(12) Subject is taking Clonidine, Alpha-blockers, Verapamil and Diltiazem, Amiodarone, Ivabradine and Anti-cholinesterase drugs.
(13) Subject is being treated for hypertension and in the opinion of the Investigator their antihypertensive medication puts them at increased risk of postural hypotension.
(14) Subject is hypotensive at screening as defined as systolic < 90 mmHg and/or diastolic <60 mmHg.
(15) Subject has clinically significant hepatic abnormalities and/or ALT and/or AST =2 x ULN and/or alkaline phosphatase (ALP) =2 x ULN and/or total bilirubin =1.5 x ULN and gamma-glutamyl transferase (GGT) =2.5 x ULN during the screening period (local laboratory results).
(16) Subject has a compression of the optic chiasm causing visual-field defects.
(17) Subject with a life expectancy of < 1 year.
(18) Subject is receiving any oestrogen-containing Hormone Replacement Therapy (HRT).
(19) Subject is receiving neuroleptic antipsychotic/antiemetic drugs.
(20) Subject has clinically significant pancreatic abnormalities and/or amylase and/or lipase =2 x ULN during the Screening period (local laboratory results).
(21) Any significant renal abnormalities, including confirmed proteinuria and/or creatinine =1.5x ULN during screening assessed by the local laboratory.
(22) Subject has any known uncontrolled cardiovascular disease or any
of the following within 6 months of Screening: ventricular or atrial dysrhythmia = common terminology criteria for adverse event (CTCAE) grade 2, bradycardia = CTCAE grade 2, electrocardiogram (ECG), QTc prolonged = CTCAE 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.
(23) Subject with history of, or known current, problems with alcohol or
drug abuse.
(24)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the pharmacodynamics of repeated administration of BIM23B065 in reducing growth hormone (GH) in subjects with acromegaly;Secondary Objective: • To assess the safety and tolerability of repeated administration of BIM23B065 in subjects with acromegaly<br>• To assess the pharmacokinetics (PK) and pharmacodynamics (PD) of repeated administration of BIM23B065<br>• To investigate the PK of BIM23B133 which is the major metabolite of BIM23B065 <br>• To assess the correlation of BIM23B065 exposure with blood pressure and heart rate (HR).;Primary end point(s): The proportion of subjects with GH =2.5µg/l or >50% reduction from mean baseline GH after 6-day titration plus 8-day treatment with BIM23B065 measured by mean serum concentration of GH over 6-hours at Day 14.;Timepoint(s) of evaluation of this end point: Day 14

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • To assess the safety and tolerability of BIM23B065<br>• To assess the proportion of subjects with GH <1.0µg/L after 6-day titration plus 8-day treatment with BIM23B065 measured by mean serum concentration of GH over 6-hours at Day 14.<br>• To investigate the PK profile of BIM23B065<br>• To correlate the PK with changes in GH, IGF-1 and PRL<br>• To determine the efficacy of BIM23B065 in reducing IGF-1 to <Upper Limit of Normal (ULN) (age normalised) after 6-day titration and 8-day treatment period at Day 14 and Day 28.<br>• To investigate the PK profile of BIM23B133<br>• To assess the correlation of exposure of BIM23B065 with blood pressure and HR.;Timepoint(s) of evaluation of this end point: Day 14, Day 28

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