Pasireotide LAR in Severe Polycystic Liver Disease

NCT01670110 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 11-007405
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Somatostatin Analogs; Polycystic Liver Disease; Autosomal Dominant Polycystic Kidney Disease; Autosomal Dominant Polycystic Liver Disease

Keywords

Polycystic Liver Disease; Autosomal dominant polycystic kidney disease; Autosomal dominant polycystic liver disease; Somatostatin analogs; Pasireotide LAR; SOM230

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (6)

• Percentage Change in Estimated Glomerular Filtration Rate (eGFR)

  Baseline, 12 months

• Percentage Change in Serum Creatinine

  Baseline, 12 months

• Percent Change in Blood Glucose

  Baseline, 12 months

• Percentage Change in Hemoglobin A1C

  Baseline, 12 months

• Percentage Change in Heart Rate

  Baseline, 12 months

Study Arms (2)

Pasireotide LAR (SOM230)

ACTIVE COMPARATOR

Active Pasireotide LAR

Drug: Pasireotide LAR

placebo injection

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Pasireotide LAR DRUG

Injectible, 60mg per month

Pasireotide LAR (SOM230)

Placebo DRUG

To be injected once per month

placebo injection

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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
• 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.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Hogan MC, Chamberlin JA, Vaughan LE, Waits AL, Banks C, Leistikow K, Oftsie T, Madsen C, Edwards M, Glockner J, Kremers WK, Harris PC, LaRusso NF, Torres VE, Masyuk TV. Pansomatostatin Agonist Pasireotide Long-Acting Release for Patients with Autosomal Dominant Polycystic Kidney or Liver Disease with Severe Liver Involvement: A Randomized Clinical Trial. Clin J Am Soc Nephrol. 2020 Sep 7;15(9):1267-1278. doi: 10.2215/CJN.13661119. Epub 2020 Aug 25.

  PMID: 32843370 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Polycystic liver disease; Polycystic Kidney, Autosomal Dominant

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Results Point of Contact

• Title: Marie C. Hogan, M.D., Ph.D.
• Organization: Mayo Clinic

Hogan.Marie@mayo.edu

507-284-3479

Study Officials

• Marie C Hogan, MD PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: August 17, 2012
• First Posted: August 21, 2012
• Study Start: August 1, 2012
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: May 1, 2020
• Results First Posted: March 2, 2020

Record last verified: 2020-04

Locations

US (1)