Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01670110
Other study ID # 11-007405
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date August 2012
Est. completion date September 2018

Study information

Verified date April 2020
Source Mayo Clinic
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to compare SOM230 treatment to placebo. The investigators will also assess the efficacy and safety of SOM230 in reducing total liver volume and improving quality of life.


Description:

Pasireotide (SOM230) is a novel multi-receptor-targeted analog that has high affinity for four of the five SST receptor subtypes (SSTr1, SSTr2, SSTr3 and SSTr5); it has a 40-fold higher affinity and 158-fold higher functional activity for the SST5 receptor than octreotide. Because of its broad receptor binding profile, pasireotide may be more potent in Polycystic Liver Disease (PLD) than octreotide. In this randomized double blind placebo controlled trial the investigators will compare SOM230 treatment to placebo for 12 months in patients with PLD. The primary endpoints will be assessed at 12 months and patients receiving placebo then crossed over to SOM230, permitting all participants to receive SOM230 for the subsequent two years. Magnetic resonance imaging (MRI) will be used to assess liver volume - the primary endpoint, which will be assessed at baseline, end of years 1 and 3. This study will assess the efficacy and safety of SOM230 in reducing total liver volume and improving quality of life over 12 months. (The investigators will not be assessing efficacy at 24 months.) The therapy way be effective in PLD but also may prove to be effective for many more patients with Polycystic Kidney Disease (PKD) which will be evaluated using eGFR and kidney volume using MRI.

The investigators plan to add other sub-sites in other locations.


Recruitment information / eligibility

Status Completed
Enrollment 48
Est. completion date September 2018
Est. primary completion date September 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years to 100 Years
Eligibility Inclusion Criteria:

- Male or female Age = 18 years.

- Diagnosis of PLD associated with ADPKD (meeting the Modified Ravine's criteria) or isolated ADPLD (defined by the criteria described by Reynolds et al)

- Severe PLD defined as a liver volume >4000mL or symptomatic disease due to mass effects from hepatic cysts (must be able to undergo MRI or CT scan to determine this).

- Not a candidate for or declining surgical intervention.

- Capable of providing informed consent.

- Life expectancy = 12 weeks

- Patients with a known history of impaired fasting blood glucose (glucose >100 and <126) may be included at the discretion of the PI. These patients should be monitored closely throughout the trial and antihyperglycemic treatment adjusted as necessary. Patients that are deemed non eligible due to elevated glucose can be re-screened after adequate medical treatment.

- Adequate end organ function as defined by:

- Adequate bone marrow function:

- WBC = 2.5 x 109/L

- Absolute Neutrophil Count (ANC) = 1.5 x 109/L

- Platelets = 100 x 109/L

- Hb = 9 g/dL

- No evidence of significant liver disease:

- Serum bilirubin =1.5 x ULN

- INR < 1.3

- ALT and AST = 2 x ULN

- Estimated glomerular filtration rate (eGFR) >30 ml/min/m2

- Serum amylase and lipase = 1.5 x ULN

- Alkaline phosphatase = 2.5 x ULN

- Written informed consent obtained prior to any screening procedures

- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures

Exclusion Criteria:

- Patients will be considered ineligible for this study if they meet any of the following criteria:

- Patients with a known hypersensitivity to SST analogs or any component of the pasireotide LAR or SQ formulations.

- Patients with known malabsorption syndrome, short bowel or chologenic diarrhea not controlled by specific therapeutic means.

- Patients with abnormal coagulation (PT or a PTT elevated by 30% above normal limits).

- Patients on continuous anticoagulation therapy. Patients who were on anticoagulant therapy must complete a washout period of at least 10 days and have confirmed normal coagulation parameters before study inclusion.

- Patients with symptomatic cholelithiasis.

- Patients who are not biochemically euthyroid.

- Patients with known history of hypothyroidism are eligible if they are on adequate and stable re-placement thyroid hormone therapy for at least 3 months.

- Serum magnesium = ULN

- QT-related exclusion criteria:

- QTcF at screening > 470 msec

- Patients with a history of syncope or family history of idiopathic sudden death

- Patients who have sustained or clinically significant cardiac arrhythmias

- Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade AV block

- Patients with concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure

- Family history of long QT syndrome

- Concomitant medications known to prolong the QT interval.

- Potassium < or = to 3.5

- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:

- Patients who have Uncontrolled diabetes as defined by HbA1c>8%* despite adequate therapy

- Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunodeficiency, including a positive HIV test result (ELISA and Western blot). An HIV test will not be required; however, previous medical history will be reviewed.

- Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with this study treatment.

- Liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis or chronic persistent hepatitis.

- Baseline ALT or AST >3x ULN

- Patients with life-threatening autoimmune and ischemic disorders.

- Uncontrolled hypertension

- Patients who have a history of a primary malignancy, with the exception of locally excised non-melanoma skin cancer and carcinoma in situ of uterine cervix. (Patients who have had no evidence of disease from primary cancer for 3 or more years are allowed to participate in the study.)

- History of pancreatitis

- Patients with a known history of hepatitis B or C

- Presence of Hepatitis B surface antigen (HbsAg)

- Presence of Hepatitis C antibody (anti-HCV)

- Patients with a history of, or current, alcohol misuse/abuse within the past 12 months

- Known gallbladder or bile duct disease, acute or chronic pancreatitis

- Patients who have any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the Investigator or the Sponsor's Medical Monitor

- Use of an investigational drug within 1 month prior to dosing

- Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Pasireotide LAR
Injectible, 60mg per month
Placebo
To be injected once per month

Locations

Country Name City State
United States Mayo Clinic Rochester Minnesota

Sponsors (1)

Lead Sponsor Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change in Liver Volume Percent change was calculated for liver volumes using the equation=[(12 month value-baseline value)/baseline value]*100*12/12 month baseline , 12 month
Primary Change in Kidney Volume Percent change was calculated for kidney volumes using the equation=[(12 month value-baseline value)/baseline value]*100*12/12 month baseline to 12 months
Secondary Percentage Change in Estimated Glomerular Filtration Rate (eGFR) eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. This value at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100 Baseline, 12 months
Secondary Percentage Change in Serum Creatinine Serum creatinine level at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100 Baseline, 12 months
Secondary Percent Change in Blood Glucose Blood glucose (mg/dLb) level at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100 Baseline, 12 months
Secondary Percentage Change in Hemoglobin A1C Hemoglobin A1C level at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100 Baseline, 12 months
Secondary Percentage Change in Heart Rate Heart rate, measured in beats per minute (BPM), at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100 Baseline, 12 months
Secondary Change in Quality of Life Measured using the SF-36 health survey, which consist of eight subscales each scored on a range of 0 to 100 (0=worst imaginable, 100=best imaginable). Change calculated from baseline = 12 month value-baseline value Baseline, 12 months
See also
  Status Clinical Trial Phase
Completed NCT02933268 - High Water Intake in Polycystic Kidney Disease N/A
Completed NCT00759369 - Water as Therapy in Autosomal Dominant Polycystic Kidney Disease (ADPKD) N/A
Completed NCT00598377 - Adrenal Functions in Autosomal Dominant Polycystic Kidney Disease N/A
Completed NCT01039987 - Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease N/A
Completed NCT03717883 - ADPKD Alterations in Hepatic Transporter Function
Recruiting NCT05193981 - A Study to Evaluate Homocysteine Metabolism and Endothelial Function in ADPKD
Completed NCT03487913 - The ELiSA Study - Evaluation of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease Phase 2
Not yet recruiting NCT06435858 - Short-term Effects of an SGLT2 Inhibitor on Divalent Ions in Autosomal Dominant Polycystic Kidney Disease Phase 4
Recruiting NCT05190744 - PB to Treat Hereditary Nephrogenic Diabetes Insipidus, ADPKD Treated With Tolvaptan, and Severely Polyuric Patients With Previous Lithium Administration Phase 2
Recruiting NCT05521191 - A Study of RGLS8429 in Patients With Autosomal Dominant Polycystic Kidney Disease Phase 1
Recruiting NCT04344769 - Characterization of the Nrf2 Response in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Active, not recruiting NCT02848521 - A Study Measuring Quality of Life, Treatment Preference and Satisfaction of ADPKD Patients in Europe
Completed NCT01451827 - 8-Week Study of Tolvaptan Dose Forms in Autosomal Dominant Polycystic Kidney Disease (ADPKD) Phase 2
Completed NCT01210560 - Dose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD Phase 2
Completed NCT01336972 - Short-term Renal Hemodynamic Effects of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD) Phase 2
Completed NCT02134899 - The Efficacy of Everolimus in Reducing Total Native Kidney Volume in Polycystic Kidney Disease Transplanted Recipients Phase 3
Active, not recruiting NCT02729662 - Efficacy of Tolvaptan on ADPKD Patients N/A
Recruiting NCT06065852 - National Registry of Rare Kidney Diseases
Recruiting NCT05288998 - Intrarenal Microvasculature in ADPKD
Recruiting NCT04939935 - Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD) Phase 3

External Links