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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-002389-62 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| lanreotide PRF | Experimental | One single dose of lanreotide PRF (via subcutaneous injection) either 180mg or 270mg or 360mg. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lanreotide PRF | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Summary of Number of Subjects With AEs. | AEs reported by the investigators using the National Cancer Institute-Common Toxicity Criteria (NCI CTCAE) classification (Version 4.03) and incidence of all reported treatment emergent AEs (TEAEs) and serious AEs (SAEs) are presented by dose cohort. AEs were assigned to a NCI CTCAE Grade from 1 through 5 as follows: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening or requiring hospitalisation; Grade 4: Life-threatening consequences; Grade 5: Death related to AE. TEAEs were defined as any AE that occurs during the active phase of the study (between the start of the 3 month treatment period and 3 months after the end of study treatment). The worst intensity of TEAES at each grade are reported for all and for related TEAES. In the event of multiple occurrences of the same AEs being reported by the same subject, the maximum intensity and the most serious causality were reported. |
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Inclusion Criteria:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Ipsen Medical Director | Ipsen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Antwerp University Hospital | Edegem | Belgium | ||||
| Domaine Universitaire Sart Tilman |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34664531 | Derived | 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. |
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Screening of subjects took place 28 to 42 days before administration of study treatment (Day -42 to Day -28). Overall, 60 subjects were screened during this run-in period; 32 of whom were screening failures and 28 subjects were enrolled and treated with lanreotide PRF.
This was an open-label, dose-ascending study to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of a single dose of lanreotide prolonged release formulation (PRF). 17 centres recruited adult subjects with acromegaly into 3 lanreotide PRF treatment cohorts (180 milligrams [mg], 270 mg and 360 mg).
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| ID | Title | Description |
|---|---|---|
| FG000 | 180 mg Lanreotide PRF | On Day 1, 3 initial subjects in Cohort 1 received 180 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. The dose escalation proceeded with a 3+3+3 scheme. If 0 or 1 out of the 3 dosed subjects had experienced a dose limiting toxicity (DLT), 3 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have been stopped and the dose declared the maximum administered dose. If ≤3 DLTs had been observed in the 9 treated subjects and the overall safety was in line with the known lanreotide safety profile, the data review committee (DRC) would have allowed the dose to be escalated to 270 mg (Cohort 2). At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until end of study (EOS) at Week 25 or early withdrawal (EW). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 16, 2016 | Sep 24, 2018 |
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| 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. |
| From Day -42 up to Week 25. |
| PK Analysis of Glycofurol Excipients: Cmax. | Blood samples for determination of the excipients (N1-glycofurol and N2-glycofurol) serum concentrations were collected at Baseline (pre-dose), at 1, 2, 4, 6, 8, 12 and 24 hours post-dose and on Days 3 and 5. Mean serum N1-glycofurol and N2-glycofurol Cmax values were determined using non-compartmental analysis. | From Baseline (pre-dose) up to Day 5. |
| PK Analysis of Glycofurol Excipients: Tmax. | Blood samples for determination of the excipients (N1-glycofurol and N2-glycofurol) serum concentrations were collected at Baseline (pre-dose), at 1, 2, 4, 6, 8, 12 and 24 hours post-dose and on Days 3 and 5. Median serum N1-glycofurol and N2-glycofurol Tmax values were determined using non-compartmental analysis. | 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). | Blood samples for determination of the excipients (N1-glycofurol and N2-glycofurol) serum concentrations were collected at Baseline (pre-dose), at 1, 2, 4, 6, 8, 12 and 24 hours post-dose and on Days 3 and 5. Mean serum N1-glycofurol and N2-glycofurol AUC0-∞ and AUC0-t values were determined using non-compartmental analysis. Only AUC0-∞ values fulfilling the accuracy determination rules were analysed. | From Baseline (pre-dose) up to Day 5. |
| PD Analysis: Mean Change From Baseline in Insulin-like Growth Factor 1 (IGF-1). | Blood samples were collected for the determination of IGF-1 in serum at Baseline (pre-dose), 6 hours post-dose and at Weeks 5, 9 and 13. Samples were also collected during follow-up at Weeks 17, 21 and 25 (or EW). Serum concentrations of IGF-1 were calculated using the Immulite 2000 Platform for all subjects in the safety population. The production of the reagent kits was stopped by the vendor during the study. The old reagent kits were used for Cohorts 1 and 2 until their expiry date and then the kits were switched to a new reagent and used for remaining subjects in Cohorts 2 and 3. Summary data for serum concentrations of IGF-1 were obtained using both methods (old and new reagent) and the mean change from Baseline at each time point is presented. | From Baseline (pre-dose) up to Week 25. |
| PD Analysis: Mean Change From Baseline in Growth Hormone (GH). | GH cycle assessments were performed by taking 5 samples in the morning (with a sample taken every 30 minutes for 2 hours) at Baseline (pre-dose), Week 5 and Week 13. Summary data for the mean of the 5 samplings of the GH cycle were generated and the mean change from Baseline at each time point is presented. | From Baseline (pre-dose) up to Week 13. |
| PD Analysis: Mean Change From Baseline in Free Triiodothyroxine (FT3) and Free Thyroxine (FT4). | Blood samples were collected for the determination of FT3 and FT4 in serum at Baseline (pre-dose) and at Weeks 2, 5, 13 and 25 (or EW). Summary data for serum concentrations of FT3 and FT4 were calculated and the mean change from Baseline at each time point is presented. | From Baseline (pre-dose) up to Week 25. |
| PD Analysis: Mean Change From Baseline in Thyroid Stimulating Hormone (TSH). | Blood samples were collected for the determination of TSH in serum at Baseline (pre-dose) and at Weeks 2, 5, 13 and 25 (or EW). Summary data for serum concentrations of TSH were calculated and the mean change from Baseline at each time point is presented. | From Baseline (pre-dose) up to Week 25. |
| PD Analysis: Mean Change From Baseline in Prolactin. | Blood samples were collected for the determination of prolactin in serum at Baseline (pre-dose) and at Weeks 2, 5, 13 and 25 (or EW). Summary data for serum concentration of prolactin were calculated and the mean change from Baseline at each time point is presented. | From Baseline (pre-dose) up to Week 25. |
| Liège |
| Belgium |
| Fakultni nemocnice u sv. Anny v Brne | Brno | Czechia |
| Fakultní nemocnice Hradec Králové (University Hospital Hradec) | Hradec Králové | Czechia |
| CHU le BOCAGE | Dijon | 21079 | France |
| Hôpital de Bicêtre (AP-HP) | Le Kremlin-Bicêtre | 94275 | France |
| CHU de la Timone | Marseille | 13385 | France |
| Hôpital Haut Lévêque | Pessac | 33604 | France |
| University Medicine Berlin | Berlin | 10117 | Germany |
| University Medical Center Hamburg-Eppendorf | Hamburg | 20246 | Germany |
| IRCCS AOU San Martino-IST, University of Genova | Genova | 16139 | Italy |
| Azienda Ospedaliera Padova | Padova | 35128 | Italy |
| Policlinico of Palermo | Palermo | 90127 | Italy |
| Ospedale Cisanello | Pisa | 56124 | Italy |
| Azienda Ospedaliera Universitaria Senese | Siena | 53100 | Italy |
| AO Città della Salute e della Scienza di Torino | Torino | 10126 | Italy |
| Lithuanian University of Health Sciences (LUHS) Kauno klinikos | Kaunas | Lithuania |
| Vilnius University hospital Santariskiu Klinikos | Vilnius | Lithuania |
| Erasmus University Medical Centre Rotterdam | Rotterdam | 3000 ca | Netherlands |
| Uniwersytecki Szpital Kliniczny w Białymstoku | Bialystok | 15-276 | Poland |
| Szpital Kliniczny im. H. Święcickiego UM w Poznaniu | Poznan | 60-355 | Poland |
| Szpital Bielanski im. ks. Jerzego Popieluszki SPZOZ | Warsaw | 01-809 | Poland |
| Szpital Kliniczny nr 1 | Wroclaw | 50-367 | Poland |
| National Institute of Endocrinology | Bucharest | 11863 | Romania |
| Kazan state Medical Academy | Kazan' | 420012 | Russia |
| Kemerovo Regional Clinical Hospital | Kemerovo | 650066 | Russia |
| Endocrinological Research Center Ministry of Health Russian Federation | Moscow | 117036 | Russia |
| Healthcare Institution | Nizhny Novgorod | 603126 | Russia |
| Federal State Budgetary Military | Saint Petersburg | 191015 | Russia |
| North-Western State Medical University | Saint Petersburg | 191015 | Russia |
| Hospital Universitario Vall d' Hebron | Barcelona | 08035 | Spain |
| Hospital Ramon y Cajal | Madrid | 28034 | Spain |
| Hospital Universitario Virgen del Rocio | Seville | 41013 | Spain |
| Queen Mary, University of London | London | EC1M 6BQ | United Kingdom |
| Christie NHS Foundation Trust | Manchester | M20 4BX | United Kingdom |
| Churchill Hospital | Oxford | OX3 7LE | United Kingdom |
| FG001 | 270 mg Lanreotide PRF | On Day 1, 1 initial subject in Cohort 2 received 270 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 2 subjects were treated and reviewed on a 1+2+2+2+2 scheme. If no DLT was experienced, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have stopped, and the dose was declared the maximum administered dose. If ≤3 DLTs had been observed in the 9 treated subjects and the overall safety was in line with the known lanreotide safety profile, the DRC would have allowed dose to be escalated to 360 mg (Cohort 3). At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
| FG002 | 360 mg Lanreotide PRF | On Day 1, 2 initial subjects in Cohort 3 received 360 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 3 subjects were treated and reviewed on a 2+2+2+3 scheme. An additional subject was also dosed in this cohort as it was considered unethical to exclude an eligible subject. If 0 or 1 subject had experienced a DLT, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have been stopped and the dose was declared the maximum administered dose. At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 180 mg Lanreotide PRF | On Day 1, 3 initial subjects in Cohort 1 received 180 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. The dose escalation proceeded with a 3+3+3 scheme. If 0 or 1 out of the 3 dosed subjects had experienced a DLT, 3 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have stopped, and the dose declared the maximum administered dose. If ≤3 DLTs had been observed in the 9 treated subjects and the overall safety was in line with the known lanreotide safety profile, the DRC would have allowed the dose to be escalated to 270 mg (Cohort 2). At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
| BG001 | 270 mg Lanreotide PRF | On Day 1, 1 initial subject in Cohort 2 received 270 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 2 subjects were treated and reviewed on a 1+2+2+2+2 scheme. If no DLT was experienced, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have stopped, and the dose was declared the maximum administered dose. If ≤3 DLTs had been observed in the 9 treated subjects and the overall safety was in line with the known lanreotide safety profile, the DRC would have allowed dose to be escalated to 360 mg (Cohort 3). At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
| BG002 | 360 mg Lanreotide PRF | On Day 1, 2 initial subjects in Cohort 3 received 360 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 3 subjects were treated and reviewed on a 2+2+2+3 scheme. An additional subject was also dosed in this cohort as it was considered unethical to exclude an eligible subject. If 0 or 1 subject had experienced a DLT, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have been stopped and the dose was declared the maximum administered dose. At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Prior Acromegaly Medication | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
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| Primary | 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. | The safety population was all subjects who received the single dose of lanreotide PRF and had at least one post baseline safety assessment. | Posted | Number | participants | From Day 1 up to Week 25. |
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| Primary | 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. | The PK valid population consisted of subjects who received at least 1 dose and had no major protocol deviations affecting the PK variables, and who had a sufficient number of serum lanreotide concentrations to estimate the main PK parameters. Only subjects with data available for analysis and who were not pre-treated with lanreotide are presented. | Posted | Mean | Standard Deviation | nanograms/millilitre (ng/mL) | From Baseline (pre-dose) up to Week 25. |
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| Primary | 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. | The PK valid population consisted of subjects who received at least 1 dose and had no major protocol deviations affecting the PK variables, and who had a sufficient number of serum lanreotide concentrations to estimate the main PK parameters. Only subjects with data available for analysis and who were not pre-treated with lanreotide are presented. | Posted | Median | Full Range | days | From Baseline (pre-dose) up to Week 25. |
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| Primary | 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. | The PK valid population consisted of subjects who received at least 1 dose and had no major protocol deviations affecting the PK variables, and who had a sufficient number of serum lanreotide concentrations to estimate the main PK parameters. Only subjects with data available for analysis and who were not pre-treated with lanreotide are presented. | Posted | Mean | Standard Deviation | days | From Baseline (pre-dose) up to Week 25. |
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| Primary | 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. | The PK valid population consisted of subjects who received at least 1 dose and had no major protocol deviations affecting the PK variables, and who had a sufficient number of serum lanreotide concentrations to estimate the main PK parameters. Only subjects with data available for analysis and who were not pre-treated with lanreotide are presented. | Posted | Mean | Standard Deviation | ng*day/mL | From Baseline (pre-dose) up to Day 85 |
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| Primary | 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. | The PK valid population consisted of subjects who received at least 1 dose and had no major protocol deviations affecting the PK variables, and who had a sufficient number of serum lanreotide concentrations to estimate the main PK parameters. Only subjects with data available for analysis and who were not pre-treated with lanreotide are presented. | Posted | Mean | Standard Deviation | ng*day/mL | From Baseline (pre-dose) up to Week 25. |
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| Secondary | Overall Summary of Number of Subjects With AEs. | AEs reported by the investigators using the National Cancer Institute-Common Toxicity Criteria (NCI CTCAE) classification (Version 4.03) and incidence of all reported treatment emergent AEs (TEAEs) and serious AEs (SAEs) are presented by dose cohort. AEs were assigned to a NCI CTCAE Grade from 1 through 5 as follows: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening or requiring hospitalisation; Grade 4: Life-threatening consequences; Grade 5: Death related to AE. TEAEs were defined as any AE that occurs during the active phase of the study (between the start of the 3 month treatment period and 3 months after the end of study treatment). The worst intensity of TEAES at each grade are reported for all and for related TEAES. In the event of multiple occurrences of the same AEs being reported by the same subject, the maximum intensity and the most serious causality were reported. | The safety population was all subjects who received the single dose of lanreotide PRF and had at least one post baseline safety assessment. | Posted | Number | participants | From Day -42 up to Week 25. |
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| Secondary | PK Analysis of Glycofurol Excipients: Cmax. | Blood samples for determination of the excipients (N1-glycofurol and N2-glycofurol) serum concentrations were collected at Baseline (pre-dose), at 1, 2, 4, 6, 8, 12 and 24 hours post-dose and on Days 3 and 5. Mean serum N1-glycofurol and N2-glycofurol Cmax values were determined using non-compartmental analysis. | The PK valid population consisted of subjects who received at least 1 dose and had no major protocol deviations affecting the PK variables, and who had a sufficient number of serum lanreotide concentrations to estimate the main PK parameters. Only subjects with data available for analysis are presented. | Posted | Mean | Standard Deviation | ng/mL | From Baseline (pre-dose) up to Day 5. |
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| Secondary | PK Analysis of Glycofurol Excipients: Tmax. | Blood samples for determination of the excipients (N1-glycofurol and N2-glycofurol) serum concentrations were collected at Baseline (pre-dose), at 1, 2, 4, 6, 8, 12 and 24 hours post-dose and on Days 3 and 5. Median serum N1-glycofurol and N2-glycofurol Tmax values were determined using non-compartmental analysis. | The PK valid population consisted of subjects who received at least 1 dose and had no major protocol deviations affecting the PK variables, and who had a sufficient number of serum lanreotide concentrations to estimate the main PK parameters. Only subjects with data available for analysis are presented. | Posted | Median | Full Range | hours | From Baseline (pre-dose) up to Day 5. |
| |||||||||||||||||||||||||||||||||
| Secondary | PK Analysis of Glycofurol Excipients: AUC0-∞ and Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Timepoint (AUC0-t). | Blood samples for determination of the excipients (N1-glycofurol and N2-glycofurol) serum concentrations were collected at Baseline (pre-dose), at 1, 2, 4, 6, 8, 12 and 24 hours post-dose and on Days 3 and 5. Mean serum N1-glycofurol and N2-glycofurol AUC0-∞ and AUC0-t values were determined using non-compartmental analysis. Only AUC0-∞ values fulfilling the accuracy determination rules were analysed. | The PK valid population consisted of subjects who received at least 1 dose and had no major protocol deviations affecting the PK variables, and who had a sufficient number of serum lanreotide concentrations to estimate the main PK parameters. | Posted | Mean | Standard Deviation | ng*h/mL | From Baseline (pre-dose) up to Day 5. |
| |||||||||||||||||||||||||||||||||
| Secondary | PD Analysis: Mean Change From Baseline in Insulin-like Growth Factor 1 (IGF-1). | Blood samples were collected for the determination of IGF-1 in serum at Baseline (pre-dose), 6 hours post-dose and at Weeks 5, 9 and 13. Samples were also collected during follow-up at Weeks 17, 21 and 25 (or EW). Serum concentrations of IGF-1 were calculated using the Immulite 2000 Platform for all subjects in the safety population. The production of the reagent kits was stopped by the vendor during the study. The old reagent kits were used for Cohorts 1 and 2 until their expiry date and then the kits were switched to a new reagent and used for remaining subjects in Cohorts 2 and 3. Summary data for serum concentrations of IGF-1 were obtained using both methods (old and new reagent) and the mean change from Baseline at each time point is presented. | The safety population was all subjects who received the single dose of lanreotide PRF and had at least one post baseline safety assessment. Only subjects with data available for analysis are presented. | Posted | Mean | Standard Deviation | ng/mL | From Baseline (pre-dose) up to Week 25. |
| |||||||||||||||||||||||||||||||||
| Secondary | PD Analysis: Mean Change From Baseline in Growth Hormone (GH). | GH cycle assessments were performed by taking 5 samples in the morning (with a sample taken every 30 minutes for 2 hours) at Baseline (pre-dose), Week 5 and Week 13. Summary data for the mean of the 5 samplings of the GH cycle were generated and the mean change from Baseline at each time point is presented. | The safety population was all subjects who received the single dose of lanreotide PRF and had at least one post baseline safety assessment. Only subjects with data available for analysis are presented. | Posted | Mean | Standard Deviation | ng/mL | From Baseline (pre-dose) up to Week 13. |
| |||||||||||||||||||||||||||||||||
| Secondary | PD Analysis: Mean Change From Baseline in Free Triiodothyroxine (FT3) and Free Thyroxine (FT4). | Blood samples were collected for the determination of FT3 and FT4 in serum at Baseline (pre-dose) and at Weeks 2, 5, 13 and 25 (or EW). Summary data for serum concentrations of FT3 and FT4 were calculated and the mean change from Baseline at each time point is presented. | The safety population was all subjects who received the single dose of lanreotide PRF and had at least one post baseline safety assessment. Only subjects with data available for analysis are presented. | Posted | Mean | Standard Deviation | picomole/litre (L) | From Baseline (pre-dose) up to Week 25. |
| |||||||||||||||||||||||||||||||||
| Secondary | PD Analysis: Mean Change From Baseline in Thyroid Stimulating Hormone (TSH). | Blood samples were collected for the determination of TSH in serum at Baseline (pre-dose) and at Weeks 2, 5, 13 and 25 (or EW). Summary data for serum concentrations of TSH were calculated and the mean change from Baseline at each time point is presented. | The safety population was all subjects who received the single dose of lanreotide PRF and had at least one post baseline safety assessment. Only subjects with data available for analysis are presented. | Posted | Mean | Standard Deviation | mIU/L | From Baseline (pre-dose) up to Week 25. |
| |||||||||||||||||||||||||||||||||
| Secondary | PD Analysis: Mean Change From Baseline in Prolactin. | Blood samples were collected for the determination of prolactin in serum at Baseline (pre-dose) and at Weeks 2, 5, 13 and 25 (or EW). Summary data for serum concentration of prolactin were calculated and the mean change from Baseline at each time point is presented. | The safety population was all subjects who received the single dose of lanreotide PRF and had at least one post baseline safety assessment. Only subjects with data available for analysis are presented. | Posted | Mean | Standard Deviation | mU/L | From Baseline (pre-dose) up to Week 25. |
|
Each subject was assessed for TEAEs over an approximate 6 month period. TEAEs were collected over the 32 month study duration.
TEAES were monitored for the safety population which was defined as all subjects who received the single dose of lanreotide PRF and had at least one post baseline safety assessment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 180 mg Lanreotide PRF | On Day 1, 3 initial subjects in Cohort 1 received 180 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. The dose escalation proceeded with a 3+3+3 scheme. If 0 or 1 out of the 3 dosed subjects had experienced a DLT, 3 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have stopped, and the dose declared the maximum administered dose. If ≤3 DLTs had been observed in the 9 treated subjects and the overall safety was in line with the known lanreotide safety profile, the DRC would have allowed the dose to be escalated to 270 mg (Cohort 2). At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. | 0 | 9 | 1 | 9 | 6 | 9 |
| EG001 | 270 mg Lanreotide PRF | On Day 1, 1 initial subject in Cohort 2 received 270 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 2 subjects were treated and reviewed on a 1+2+2+2+2 scheme. If no DLT was experienced, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have stopped, and the dose was declared the maximum administered dose. If ≤3 DLTs had been observed in the 9 treated subjects and the overall safety was in line with the known lanreotide safety profile, the DRC would have allowed dose to be escalated to 360 mg (Cohort 3). At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. | 0 | 9 | 0 | 9 | 7 | 9 |
| EG002 | 360 mg Lanreotide PRF | On Day 1, 2 initial subjects in Cohort 3 received 360 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 3 subjects were treated and reviewed on a 2+2+2+3 scheme. An additional subject was also dosed in this cohort as it was considered unethical to exclude an eligible subject. If 0 or 1 subject had experienced a DLT, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have been stopped and the dose was declared the maximum administered dose. At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. | 0 | 10 | 1 | 10 | 7 | 10 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Faeces Soft | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Inguinal Hernia | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Influenza Like Illness | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Injection Site Pain | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Injection Site Haematoma | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Injection Site Induration | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Injection Site Swelling | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Respiratory Tract Infection Viral | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Viral Upper Respiratory Tract Infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Flank Pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Iron Deficiency Anaemia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Orthostatic Hypotension | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Vasculitis | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Vision Blurred | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Conjunctival Hyperaemia | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Blood Bilirubin Increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Sinus Bradycardia | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Breast Pain | Reproductive system and breast disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Postmenopausal Haemorrhage | Reproductive system and breast disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Renal Cyst | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
|
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.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Ipsen | Use email address below | clinical.trials@ipsen.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 11, 2017 | Sep 24, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000172 | Acromegaly |
| ID | Term |
|---|---|
| D001849 | Bone Diseases, Endocrine |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D006964 | Hyperpituitarism |
| D010900 | Pituitary Diseases |
| D007027 | Hypothalamic Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C060347 | lanreotide |
Not provided
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Lanreotide Autogel |
|
| OG002 | Lanreotide PK Set: 360 mg Lanreotide PRF | The lanreotide PK dataset included 6 subjects from the PK valid population who were not pre-treated with lanreotide and who received 1 deep subcutaneous injection of 360 mg lanreotide PRF. The 3 subjects previously treated with a stable dose of lanreotide Autogel were expected to have a detectable pre-dose concentration and it was considered relevant to exclude them. |
|
|
| OG002 | Lanreotide PK Set: 360 mg Lanreotide PRF | The lanreotide PK dataset included the 6 subjects from the PK valid population who were not pre-treated with lanreotide and who received 1 deep subcutaneous injection of 360 mg lanreotide PRF. The 3 subjects previously treated with a stable dose of lanreotide Autogel were expected to have a detectable pre-dose concentration and it was considered relevant to exclude them. |
|
|
| OG002 | Lanreotide PK Set: 360 mg Lanreotide PRF | The lanreotide PK dataset included the 6 subjects from the PK valid population who were not pre-treated with lanreotide and who received 1 deep subcutaneous injection of 360 mg lanreotide PRF. The 3 subjects previously treated with a stable dose of lanreotide Autogel were expected to have a detectable pre-dose concentration and it was considered relevant to exclude them. |
|
|
| OG002 | Lanreotide PK Set: 360 mg Lanreotide PRF | The lanreotide PK dataset included the 6 subjects from the PK valid population who were not pre-treated with lanreotide and who received 1 deep subcutaneous injection of 360 mg lanreotide PRF. The 3 subjects previously treated with a stable dose of lanreotide Autogel were expected to have a detectable pre-dose concentration and it was considered relevant to exclude them. |
|
|
| OG002 | Lanreotide PK Set: 360 mg Lanreotide PRF | The lanreotide PK dataset included the 6 subjects from the PK valid population who were not pre-treated with lanreotide and who received 1 deep subcutaneous injection of 360 mg lanreotide PRF. The 3 subjects previously treated with a stable dose of lanreotide Autogel were expected to have a detectable pre-dose concentration and it was considered relevant to exclude them. |
|
|
| OG001 | 270 mg Lanreotide PRF | On Day 1, 1 initial subject in Cohort 2 received 270 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 2 subjects were treated and reviewed on a 1+2+2+2+2 scheme. If no DLT was experienced, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have stopped, and the dose was declared the maximum administered dose. If ≤3 DLTs had been observed in the 9 treated subjects and the overall safety was in line with the known lanreotide safety profile, the DRC would have allowed dose to be escalated to 360 mg (Cohort 3). At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
| OG002 | 360 mg Lanreotide PRF | On Day 1, 2 initial subjects in Cohort 3 received 360 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 3 subjects were treated and reviewed on a 2+2+2+3 scheme. An additional subject was also dosed in this cohort as it was considered unethical to exclude an eligible subject. If 0 or 1 subject had experienced a DLT, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have been stopped and the dose was declared the maximum administered dose. At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
|
|
| OG002 | Glycofurol PK Set: 360 mg Lanreotide PRF | Due to bioanalytical issues, no results for the excipient N1-glycofurol and N2-glycofurol for this cohort were available at the time of the PK analysis. |
|
|
| OG002 | Glycofurol PK Set: 360 mg Lanreotide PRF | Due to bioanalytical issues, no results for the excipient N1-glycofurol and N2-glycofurol for this cohort were available at the time of the PK analysis. |
|
|
| OG002 | Glycofurol PK Set: 360 mg Lanreotide PRF | Due to bioanalytical issues, no results for the excipient N1-glycofurol and N2-glycofurol for this cohort were available at the time of the PK analysis. |
|
|
| OG001 | 270 mg Lanreotide PRF | On Day 1, 1 initial subject in Cohort 2 received 270 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 2 subjects were treated and reviewed on a 1+2+2+2+2 scheme. If no DLT was experienced, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have stopped, and the dose was declared the maximum administered dose. If ≤3 DLTs had been observed in the 9 treated subjects and the overall safety was in line with the known lanreotide safety profile, the DRC would have allowed dose to be escalated to 360 mg (Cohort 3). At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
| OG002 | 360 mg Lanreotide PRF | On Day 1, 2 initial subjects in Cohort 3 received 360 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 3 subjects were treated and reviewed on a 2+2+2+3 scheme. An additional subject was also dosed in this cohort as it was considered unethical to exclude an eligible subject. If 0 or 1 subject had experienced a DLT, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have been stopped and the dose was declared the maximum administered dose. At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
|
|
| 270 mg Lanreotide PRF |
On Day 1, 1 initial subject in Cohort 2 received 270 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 2 subjects were treated and reviewed on a 1+2+2+2+2 scheme. If no DLT was experienced, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have stopped, and the dose was declared the maximum administered dose. If ≤3 DLTs had been observed in the 9 treated subjects and the overall safety was in line with the known lanreotide safety profile, the DRC would have allowed dose to be escalated to 360 mg (Cohort 3). At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
| OG002 | 360 mg Lanreotide PRF | On Day 1, 2 initial subjects in Cohort 3 received 360 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 3 subjects were treated and reviewed on a 2+2+2+3 scheme. An additional subject was also dosed in this cohort as it was considered unethical to exclude an eligible subject. If 0 or 1 subject had experienced a DLT, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have been stopped and the dose was declared the maximum administered dose. At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
|
|
| 270 mg Lanreotide PRF |
On Day 1, 1 initial subject in Cohort 2 received 270 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 2 subjects were treated and reviewed on a 1+2+2+2+2 scheme. If no DLT was experienced, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have stopped, and the dose was declared the maximum administered dose. If ≤3 DLTs had been observed in the 9 treated subjects and the overall safety was in line with the known lanreotide safety profile, the DRC would have allowed dose to be escalated to 360 mg (Cohort 3). At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
| OG002 | 360 mg Lanreotide PRF | On Day 1, 2 initial subjects in Cohort 3 received 360 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 3 subjects were treated and reviewed on a 2+2+2+3 scheme. An additional subject was also dosed in this cohort as it was considered unethical to exclude an eligible subject. If 0 or 1 subject had experienced a DLT, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have been stopped and the dose was declared the maximum administered dose. At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
|
|
On Day 1, 1 initial subject in Cohort 2 received 270 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 2 subjects were treated and reviewed on a 1+2+2+2+2 scheme. If no DLT was experienced, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have stopped, and the dose was declared the maximum administered dose. If ≤3 DLTs had been observed in the 9 treated subjects and the overall safety was in line with the known lanreotide safety profile, the DRC would have allowed dose to be escalated to 360 mg (Cohort 3). At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
| OG002 | 360 mg Lanreotide PRF | On Day 1, 2 initial subjects in Cohort 3 received 360 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 3 subjects were treated and reviewed on a 2+2+2+3 scheme. An additional subject was also dosed in this cohort as it was considered unethical to exclude an eligible subject. If 0 or 1 subject had experienced a DLT, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have been stopped and the dose was declared the maximum administered dose. At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
|
|
On Day 1, 1 initial subject in Cohort 2 received 270 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 2 subjects were treated and reviewed on a 1+2+2+2+2 scheme. If no DLT was experienced, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have stopped, and the dose was declared the maximum administered dose. If ≤3 DLTs had been observed in the 9 treated subjects and the overall safety was in line with the known lanreotide safety profile, the DRC would have allowed dose to be escalated to 360 mg (Cohort 3). At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
| OG002 | 360 mg Lanreotide PRF | On Day 1, 2 initial subjects in Cohort 3 received 360 mg lanreotide PRF by a single deep subcutaneous injection in the superior, external quadrant of the buttock and a 12-week treatment period then commenced. Cohort 3 subjects were treated and reviewed on a 2+2+2+3 scheme. An additional subject was also dosed in this cohort as it was considered unethical to exclude an eligible subject. If 0 or 1 subject had experienced a DLT, 2 more subjects would have been dosed with the same dose. If more than 3 out of 9 subjects had experienced a DLT, dose escalation would have been stopped and the dose was declared the maximum administered dose. At the end of the treatment period subjects continued to be assessed over a 12-week follow up period until EOS at Week 25 or EW. |
|
|