NCT00171730

An Extension Study to Assess the Long-Term Safety and Efficacy of Pasireotide in Participants With Acromegaly

Completed Phase 2 Results posted Last updated 5 September 2021

What this trial tests

Phase 2 trial testing Pasireotide in Acromegaly in 30 participants. Completed in 6 December 2013.

Timeline

24 August 2004

Primary endpoint
6 December 2013

6 December 2013

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	30
Start date	24 August 2004
Primary completion	6 December 2013
Estimated completion	6 December 2013
Sites	10 locations across France, Italy, Belgium, Germany, Switzerland, Australia, United States

Drugs / interventions tested

• Pasireotide (PASIREOTIDE) — full drug profile →

Conditions studied

• Acromegaly — all drugs for Acromegaly →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 80, any sex, with Acromegaly. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) Observed Response by Dose Class Primary · Month 9 (Month 9 visit is at the completion of six months in this extension study)

A participant was a responder to a dose level if the mean GH level after dosing (t30, t60, t90, and t120) was below/equal to 2.5 microgram/litre (μg/L), and if the mean of IGF-1 of the two pre-dose values (t-30, t-1) was within normal limits for age-sex matched controls. If three or more of t30, t60, t90, or t120 were missing, mean GH was considered missing. If either t-30 or t-1 was missing, mean IGF-1 was considered missing. Pasireotide incident dose classes were defined by total daily doses ranges (\<1200 μg/d, 1200 to \<1500 μg/d, ≥ 1500 μg/d).

Group	Value	95% CI
Pasireotide s.c. <1200 μg/d	20	9.0 – 43.6
Pasireotide s.c. 1200 to <1500 μg/d	28.6	9.0 – 43.6
Pasireotide s.c. ≥1500 μg/d	14.3	9.0 – 43.6
Pasireotide s.c. Overall	23.1	9.0 – 43.6

Time to Tumor Response Secondary · Core study baseline to at least a 20% decrease in pituitary tumor volume (up to approximately 114 months)

Time to tumor response was defined as time from Sandostatin baseline (core study baseline) to at least 20% decrease in tumor volume.

Group	Value	95% CI
Pasireotide s.c. Overall	12.2	4.9 – 19.2

Summary Magnetic Resonance Imaging (MRI) Pituitary Tumor Volumes Secondary · Core study baseline, Months 9, 27, 63, 75 and 99

Pituitary Tumor Volumes were assessed by MRI. Core study baseline was defined as the last non-missing observation prior to the start of Sandostatin s.c. treatment.

Core Study Baseline

Group	Value	95% CI
Pasireotide s.c. Overall	4457.4	± 4891.98

Month 9

Group	Value	95% CI
Pasireotide s.c. Overall	2839.3	± 2710.61

Month 27

Group	Value	95% CI
Pasireotide s.c. Overall	2536	± 2219.13

Month 63

Group	Value	95% CI
Pasireotide s.c. Overall	456	± 381.84

Month 75

Group	Value	95% CI
Pasireotide s.c. Overall	1016	± 872.39

Month 99

Group	Value	95% CI
Pasireotide s.c. Overall	180	± NA

Percentage of Participants With Symptoms of Acromegaly Secondary · Core study baseline till the last assessment of the extension study (up to approximately 114 months)

Participants scored the following symptoms of acromegaly: Headache, perspiration, paresthesia, fatigue, osteoarthralgia, and carpal tunnel syndrome on a 5-point scale (0 = None/absent, 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Very severe).

Headache - 0

Group	Value	95% CI
Pasireotide s.c. Overall	46.7

Headache - 1

Group	Value	95% CI
Pasireotide s.c. Overall	26.7

Headache - 2

Group	Value	95% CI
Pasireotide s.c. Overall	6.7

Headache - 3

Group	Value	95% CI
Pasireotide s.c. Overall	0

Headache - 4

Group	Value	95% CI
Pasireotide s.c. Overall	0

Headache - Not Done

Group	Value	95% CI
Pasireotide s.c. Overall	20

Perspiration - 0

Group	Value	95% CI
Pasireotide s.c. Overall	20

Perspiration - 1

Group	Value	95% CI
Pasireotide s.c. Overall	33.3

Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation Secondary · Core study baseline till the last assessment of the extension study (up to approximately 114 months)

Sleep apnea symptoms were assessed using the Epworth Sleepiness Scale (ESS). The ESS is a self-administered questionnaire with 8 questions. It provides a measure of a person's general level of daytime sleepiness, or average sleep propensity in daily life. Percentage of participants were reported in 8 different situations: sitting and reading; watching TV; sitting, inactive in a public place; passenger in a car, an hour without break; lying down to rest in the afternoon; sitting and talking to someone; sitting quietly after a lunch without alcohol; and in a car, stopped a few minutes in the tra

Sitting and Reading - 0

Group	Value	95% CI
Pasireotide s.c. Overall	36.7

Sitting and Reading - 1

Group	Value	95% CI
Pasireotide s.c. Overall	23.3

Sitting and Reading - 2

Group	Value	95% CI
Pasireotide s.c. Overall	23.3

Sitting and Reading - 3

Group	Value	95% CI
Pasireotide s.c. Overall	0

Sitting and Reading - Not Done

Group	Value	95% CI
Pasireotide s.c. Overall	16.7

Watching TV - 0

Group	Value	95% CI
Pasireotide s.c. Overall	23.3

Watching TV - 1

Group	Value	95% CI
Pasireotide s.c. Overall	33.3

Watching TV - 2

Group	Value	95% CI
Pasireotide s.c. Overall	23.3

Percentage of Participants With One or More Adverse Events (AEs) Secondary · From start of study drug treatment up to end of study (approximately 111 months)

An AE was any undesirable sign, symptom or medical condition that occurred after starting study drug even if the event was not considered to be related to study drug. Percentage of participants with any AE were categorized by pasireotide incident dose classes, which were defined by total daily doses ranges (\<1200 μg/d, 1200 to \<1500 μg/d, ≥ 1500 μg/d).

Group	Value	95% CI
Pasireotide s.c. <1200 μg/d	80.0
Pasireotide s.c. 1200 to <1500 μg/d	86.7
Pasireotide s.c. ≥1500 μg/d	91.7

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious Adverse Events were monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until Last Participant Last Visit (approximately 111 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pasireotide s.c. <1200 μg/d

Serious: 3/30 (10%)

Deaths: 0/30

Pasireotide s.c. 1200 to <1500 μg/d

Serious: 4/30 (13%)

Deaths: 0/30

Pasireotide s.c. ≥1500 μg/d

Serious: 2/12 (17%)

Deaths: 0/12

Serious adverse events (13 terms)

Reaction	System	Pasireotide s.c. <1200 μg/d	Pasireotide s.c. 1200 to <…	Pasireotide s.c. ≥1500 μg/d
Hyperglycemia	Metabolism and nutrition disorders	—	—	—
Acromegaly	Endocrine disorders	—	—	—
Blindness	Eye disorders	—	—	—
Cholecystitis chronic	Hepatobiliary disorders	—	—	—
Laryngitis	Infections and infestations	—	—	—
Pilonidal cyst	Infections and infestations	—	—	—
Tracheobronchitis	Infections and infestations	—	—	—
Tracheal obstruction	Injury, poisoning and procedural complications	—	—	—
Diabetes mellitus	Metabolism and nutrition disorders	—	—	—
Arthropathy	Musculoskeletal and connective tissue disorders	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—
Mucoepidermoid carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Panic attack	Psychiatric disorders	—	—	—

Other adverse events (65 terms — click to expand)

Reaction	System	Pasireotide s.c. <1200 μg/d	Pasireotide s.c. 1200 to <…	Pasireotide s.c. ≥1500 μg/d
Diarrhoea	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—
Cholelithiasis	Hepatobiliary disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Diabetes mellitus	Metabolism and nutrition disorders	—	—	—
Fatigue	General disorders	—	—	—
Depression	Psychiatric disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Hyperhidrosis	Skin and subcutaneous tissue disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Type 2 diabetes mellitus	Metabolism and nutrition disorders	—	—	—
Bronchitis	Infections and infestations	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Influenza	Infections and infestations	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Hypertension	Vascular disorders	—	—	—
Chest pain	General disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Incision site pain	Injury, poisoning and procedural complications	—	—	—
Tremor	Nervous system disorders	—	—	—
Paraesthesia	Nervous system disorders	—	—	—
Haemorrhoids	Gastrointestinal disorders	—	—	—
Oesophageal spasm	Gastrointestinal disorders	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—
Nephrolithiasis	Renal and urinary disorders	—	—	—
Haematuria	Renal and urinary disorders	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	—	—	—
Hypoglycaemia	Metabolism and nutrition disorders	—	—	—
Inguinal hernia repair	Surgical and medical procedures	—	—	—
Haemangioma of liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Asthenia	General disorders	—	—	—

Most-reported serious reactions: Hyperglycemia, Acromegaly, Blindness, Cholecystitis chronic, Laryngitis, Pilonidal cyst, Tracheobronchitis, Tracheal obstruction.

Data from ClinicalTrials.gov NCT00171730 adverse events section.

Sponsor's own description

Acromegaly is a rare, serious condition characterized by chronic hypersecretion of growth hormone (GH), generally caused by a GH-secreting pituitary adenoma. The study assessed the long-term safety and efficacy of pasireotide in participants with acromegaly.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Long-term efficacy and safety of subcutaneous pasireotide in acromegaly: results from an open-ended, multicenter, Phase II extension study.
   Petersenn S, Farrall AJ, De Block C, Melmed S, et al · · 2014 · cited 32× · PMID 23529827 · DOI 10.1007/s11102-013-0478-0
2. Therapeutic options in the management of acromegaly: focus on lanreotide Autogel.
   Roelfsema F, Biermasz NR, Pereira AM, Romijn JA. · · 2008 · cited 14× · PMID 19707377 · DOI 10.2147/btt.s3356