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NCT01915303

Study of the Efficacy and Safety of Pasireotide s.c. +/- Cabergoline in Patients With Cushing's Disease

Terminated Phase 2 Results posted Last updated 18 September 2020
What this trial tests

Phase 2 trial testing Pasireotide with or without cabergoline in Cushings Disease in 68 participants. Terminated before completion.

Timeline
6 March 2014
Primary endpoint
5 September 2016
4 September 2019

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment68
Start date6 March 2014
Primary completion5 September 2016
Estimated completion4 September 2019
Sites29 locations across France, Colombia, Italy, Netherlands, Greece, Malaysia, Belgium, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Cushings Disease. 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 Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN Collected or Imputed at Week 35 Primary · Baseline up to week 35

Participants who attained mUFC ≤ 1.0 x ULN (upper limit of normal) with pasireotide alone or in combination with cabergoline. The 24h-UFC concentration results from three samples, collected during the screening period, were averaged to obtain the Baseline urinary free cortisol level. mean 24h-UFC was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit. Imputation: subjects who completed the end of treatment visit at Week 35, but had missing evaluation of mean urinary free cortisol (mUFC). The last available mUFC assessment at or after

GroupValue95% CI
All Patients50.037.6 – 62.4
Mean Urinary Free Cortisol (mUFC) at Scheduled Visits Secondary · Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

Mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.

Baseline
GroupValue95% CI
All Patients501.6± 488.66
Core Week 2 n-8
GroupValue95% CI
All Patients217.0± 100.69
Core Week 4 n=59
GroupValue95% CI
All Patients242.1± 203.47
Core Week 8 n=58
GroupValue95% CI
All Patients230.0± 195.21
Core Week 13 n=51
GroupValue95% CI
All Patients231.0± 240.98
Core Week 17 n=57
GroupValue95% CI
All Patients310.3± 429.64
Core Week 22 n=50
GroupValue95% CI
All Patients214.0± 202.80
Core Week 26 n=54
GroupValue95% CI
All Patients211.6± 173.58
Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN Secondary · Baseline up to week 235

Actual mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.

Baseline
GroupValue95% CI
All Patients4.40.9 – 12.4
Core Week 17 n=57
GroupValue95% CI
All Patients28.117.0 – 41.5
Core Week 35 n=45
GroupValue95% CI
All Patients48.933.7 – 64.2
Ext Week 43 n=22
GroupValue95% CI
All Patients63.640.7 – 82.8
Ext Week 67 n=17
GroupValue95% CI
All Patients47.123.0 – 72.2
Ext Week 91 n=18
GroupValue95% CI
All Patients61.135.7 – 82.7
Ext Week 115 n=13
GroupValue95% CI
All Patients76.946.2 – 95.0
Ext Week 139 n=9
GroupValue95% CI
All Patients77.840.0 – 97.2
Percentage of Participants Who Attain mUFC ≤ 1.0 x ULN or Have at Least 50% Reduction From Baseline in mUFC Secondary · Baseline up to week 235

Actual mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.

Baseline
GroupValue95% CI
All Patients4.40.9 – 12.4
Core Week 17 n=57
GroupValue95% CI
All Patients54.440.7 – 67.6
Core Week 35 n=45
GroupValue95% CI
All Patients68.953.4 – 81.8
Ext Week 43 n=22
GroupValue95% CI
All Patients86.465.1 – 97.1
Ext Week 67 n=17
GroupValue95% CI
All Patients76.550.1 – 93.2
Ext Week 91 n=18
GroupValue95% CI
All Patients83.358.6 – 96.4
Ext Week 115 n=13
GroupValue95% CI
All Patients92.364.0 – 99.8
Ext Week 139 n=9
GroupValue95% CI
All Patients77.840.0 – 97.2
Duration (Weeks) of Controlled or Partially Controlled Response Secondary · from the date patient's first normalization (mUFC ≤ 1.0xULN) or at least 50% reduction from baseline up to the date when the patient's mUFC > 1.0 x ULN

Duration of controlled or partially controlled response is defined as the period starting from the date of patient's first normalization (mUFC ≤ 1.0 x ULN) or at least 50% reduction from baseline up to the date when the patient's mUFC \> 1.0 x ULN and the reduction from baseline falls to less than 50% from the first time

Core n=36
GroupValue95% CI
All Patients13.19.3 – 22.4
Extension n=20
GroupValue95% CI
All Patients22.08.1 – 70.1
Plasma Adrenocorticotropic Hormone (ACTH) Secondary · Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

A pre-dose blood draw for plasma ACTH sampling was taken at visits. Samples were analyzed by a central laboratory.

Baseline
GroupValue95% CI
All Patients16.3± 16.3
Core Week 2 n-62
GroupValue95% CI
All Patients12.4± 9.91
Core Week 4 n=63
GroupValue95% CI
All Patients14.2± 12.50
Core Week 8 n=61
GroupValue95% CI
All Patients13.3± 11.90
Core Week 13 n=53
GroupValue95% CI
All Patients11.9± 10.98
Core Week 17 n=58
GroupValue95% CI
All Patients12.3± 9.03
Core Week 22 n=49
GroupValue95% CI
All Patients13.7± 13.82
Core Week 26 n=55
GroupValue95% CI
All Patients12.4± 12.09
Serum Cortisol Levels Secondary · Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

A pre-dose blood draw for an 8 am fasting serum cortisol measurement were taken at visits. Samples were analyzed by a central laboratory.

Baseline
GroupValue95% CI
All Patients738.6± 332.53
Core Week 2 n-62
GroupValue95% CI
All Patients626.1± 281.57
Core Week 4 n=64
GroupValue95% CI
All Patients663.6± 292.38
Core Week 8 n=61
GroupValue95% CI
All Patients649.0± 297.11
Core Week 13 n=53
GroupValue95% CI
All Patients628.8± 269.43
Core Week 17 n=58
GroupValue95% CI
All Patients683.0± 282.28
Core Week 22 n=49
GroupValue95% CI
All Patients625.4± 216.29
Core Week 26 n=55
GroupValue95% CI
All Patients632.7± 278.75
Sitting Systolic Blood Pressure at Week 35 Secondary · Baseline and week 35

The mean arterial blood pressure determinations were obtained in the sitting position. Three measurements were taken with 5 minute intervals and the mean was used for study specific procedures

Baseline
GroupValue95% CI
All Patients125.9± 14.3
Week 35 n=41
GroupValue95% CI
All Patients119.5± 18.6
Sitting Diastolic Blood Pressure at Week 35 Secondary · Baseline and week 35

The mean arterial blood pressure determinations were obtained in the sitting position. Three measurements were taken with 5 minute intervals and the mean was used for study specific procedures

Baseline
GroupValue95% CI
All Patients81.8± 9.12
Week 35 n=41
GroupValue95% CI
All Patients77.2± 12.42
Body Weight at Week 35 Secondary · Baseline and week 35

Weight was was one of the measures of clinical symptoms of CD

Baseline
GroupValue95% CI
All Patients82.2± 19.1
Week 35 n=41
GroupValue95% CI
All Patients75.6± 20.4
Body Mass Index at Week 35 Secondary · Baseline and week 35

Body mass index was one of the measurements of clinical symptoms of CD. Body mass index=weight in kg divided by the square of the body height (in meters)

Baseline
GroupValue95% CI
All Patients31.3± 6.6
Week 35 n=41
GroupValue95% CI
All Patients28.4± 6.8
Waist Circumference at Week 35 Secondary · Baseline and week 35

Waist circumference was one of the measurements of clinical signs of CD

Baseline
GroupValue95% CI
All Patients104.1± 19.1
Week 35 n=41
GroupValue95% CI
All Patients99.1± 18.2

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment, up to maximum duration of 272 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

All Patients
Serious: 15/68 (22%)
Deaths: 3/68

Serious adverse events (33 terms)

ReactionSystemAll Patients
Abdominal painGastrointestinal disorders
CholelithiasisHepatobiliary disorders
AnaemiaBlood and lymphatic system disorders
Coronary artery diseaseCardiac disorders
Glucocorticoid deficiencyEndocrine disorders
Intra-abdominal haematomaGastrointestinal disorders
DeathGeneral disorders
Multiple organ dysfunction syndromeGeneral disorders
Bile duct stoneHepatobiliary disorders
CholecystitisHepatobiliary disorders
Abscess limbInfections and infestations
CellulitisInfections and infestations
VaricellaInfections and infestations
Hip fractureInjury, poisoning and procedural complications
Muscle ruptureInjury, poisoning and procedural complications
Radius fractureInjury, poisoning and procedural complications
WoundInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
Diabetes mellitusMetabolism and nutrition disorders
HypoglycaemiaMetabolism and nutrition disorders
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
Bladder neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (45 terms — click to expand)

ReactionSystemAll Patients
NauseaGastrointestinal disorders
HyperglycaemiaMetabolism and nutrition disorders
DiarrhoeaGastrointestinal disorders
CholelithiasisHepatobiliary disorders
HeadacheNervous system disorders
DizzinessNervous system disorders
FatigueGeneral disorders
Back painMusculoskeletal and connective tissue disorders
Diabetes mellitusMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
NasopharyngitisInfections and infestations
Gamma-glutamyltransferase increasedInvestigations
HypoglycaemiaMetabolism and nutrition disorders
AlopeciaSkin and subcutaneous tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
DepressionPsychiatric disorders
RashSkin and subcutaneous tissue disorders
AstheniaGeneral disorders
InsomniaPsychiatric disorders
AnaemiaBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders
Oedema peripheralGeneral disorders
Urinary tract infectionInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
Vitamin D deficiencyMetabolism and nutrition disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Mitral valve incompetenceCardiac disorders
Alanine aminotransferase increasedInvestigations
HypercholesterolaemiaMetabolism and nutrition disorders
HypertriglyceridaemiaMetabolism and nutrition disorders
HyperuricaemiaMetabolism and nutrition disorders
HypertensionVascular disorders
BradycardiaCardiac disorders
FlatulenceGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Hepatic steatosisHepatobiliary disorders
InfluenzaInfections and infestations

Most-reported serious reactions: Abdominal pain, Cholelithiasis, Anaemia, Coronary artery disease, Glucocorticoid deficiency, Intra-abdominal haematoma, Death, Multiple organ dysfunction syndrome.

Data from ClinicalTrials.gov NCT01915303 adverse events section.

Sponsor's own description

The main purpose of this prospective, multicenter, open-label phase II study, was to evaluate the efficacy and safety of pasireotide alone or in combination with cabergoline in patients with Cushing's disease.

Publications & conference data

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

  1. Medical Treatment of Cushing's Disease: An Overview of the Current and Recent Clinical Trials.
    Pivonello R, Ferrigno R, De Martino MC, Simeoli C, et al · · 2020 · cited 84× · PMID 33363514 · DOI 10.3389/fendo.2020.00648
  2. Individualized medical treatment options in Cushing disease.
    Gilis-Januszewska A, Bogusławska A, Rzepka E, Ziaja W, et al · · 2022 · cited 23× · PMID 36531477 · DOI 10.3389/fendo.2022.1060884
  3. Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing's disease.
    Feelders RA, Fleseriu M, Kadioglu P, Bex M, et al · · 2023 · cited 16× · PMID 37876540 · DOI 10.3389/fendo.2023.1165681
  4. Update and Practical Recommendations for the Use of Medical Treatment of Cushing Syndrome.
    Araujo-Castro M, Lamas C, Nowak E, Newell-Price J, et al · · 2026 · cited 1× · PMID 41489578 · DOI 10.1210/endrev/bnaf042

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing