A Phase l Study to Evaluate the Pharmacokinetics and Safety Pasireotide in Subjects With Varying Degrees of Renal Impairment Compared to Healthy Volunteers

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01578928
First received: April 12, 2012
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to assess the effect of renal impairment on the pharmacokinetics (PK) of pasireotide,the PK of pasireotide in subjects with different degrees of renal impairment.


Condition Intervention Phase
Renal Impairment
Drug: SOM230
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Multicenter, Single Dose Study to Evaluate the Pharmacokinetics and Safety of Subcutaneous (s.c.) Pasireotide in Subjects With Varying Degrees of Renal Impairment Compared to a Matched Control Group of Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Plasma and Urine PK parameters [ Time Frame: pre-dose (-1 min) and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12, 24, 36, 48, 72, 96, 120 and 122 hours post-dose ] [ Designated as safety issue: Yes ]
    Description: Cmax, AUCinf, AUClast, CL/F, CLR, glucose, insulin, glucagon


Secondary Outcome Measures:
  • Additional PK parameters [ Time Frame: pre-dose (-1 min) and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 24, 36, 48, 72, 96, 120 and 122 hours post-dose ] [ Designated as safety issue: Yes ]
    Description: Vz/F, T1/2, Fu, Cmax,u, AUCinf,u, AUClast,u, CLu/F and Vu/F


Estimated Enrollment: 64
Study Start Date: May 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SOM230
subjects with varying degrees of renal impairment along with subjects without renal impairment
Drug: SOM230

Detailed Description:

This is a phase I, open-label, multicenter, single dose study to evaluate the PK and safety of pasireotide s.c. injection in subjects with varying degrees of renal impairment compared to healthy subjects with normal renal function. Subjects will be classified by their respective degree of renal functions (normal, mild, moderate, severe, and ESRD (End Stage Renal Disease) according to eGFR as determined at the screening visit.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

Subjects eligible for inclusion in this study have to meet all of the following criteria:

  1. Written informed consent obtained prior to any screening procedures.
  2. Subjects must be able to communicate well with the investigator and comply with the requirements of the study procedures
  3. Male or female subjects between 18 and 75 years of age, inclusive.
  4. Vital Signs at screening and baseline which are within the following ranges:

    • Oral body temperature: ≥ 35.0 and ≤ 37.5 ˚C
    • Pulse rate: 40-90 bpm
  5. Subjects must have a BMI between 20 kg/m2 and 30 kg/m2 and weigh at least 50 kg and no more than 120 kg.
  6. Subjects must be willing to comply with dietary, fluid, and lifestyle restrictions (from day-1 to study completion).
  7. Other than renal impairment, subjects must be stable and appropriately managed relative to chronic diseases (such as diabetes and hypertension) as determined by past medical history, physical examination, electrocardiogram, and laboratory tests for chemistry and hematology.

    For renal impairment subjects only

  8. Subjects must have stable renal disease without evidence of renal progressive disease (stable renal disease is defined as no significant change, such as, stable eGFR, for 12 weeks prior to study entry).
  9. Blood pressure (3 minutes resting before measurement) in the supine position:

    • Systolic: 90-165 mmHg
    • Diastolic: 60-110 mmHg

    For control subjects only

  10. Subjects must be matched to at least one renal impaired subject by gender, age (±10 years), body weight (±20%), BMI (±5%) and race.
  11. Blood pressure (3 minutes resting before measurement) in the supine position:

    • Systolic: 90-140 mmHg
    • Diastolic: 50-90 mmHg

Exclusion criteria:

Subjects eligible for this study must not meet any of the following criteria:

  1. Clinically significant abnormal laboratory values at the screening evaluation or at the baseline re-evaluation, excluding those normally associated with mild to severe degree of renal impairment or the primary cause of renal insufficiency
  2. Use of any over-the-counter medications or vitamins or herbal/natural supplements during 2 weeks prior to dosing (acetaminophen is acceptable, and must be documented in the Concomitant Medications/Non-Drug Therapies page of the CRF)
  3. Current medical history of the following:

    • Sustained or clinically significant cardiac arrhythmias
    • History of syncope or family history of idiopathic sudden death
    • Risk factors for torsades de pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high grade AV block
    • Screening QTcF > 450ms
    • 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
    • Concomitant medications known to increase the QT interval
  4. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation
  5. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing or other amount considered to compromise the health of the subject if previous history of anemia exists
  6. Significant acute illness within the two weeks prior to dosing
  7. History of immunocompromise, including a positive HIV (ELISA and Western blot) test result
  8. History of allergies to the investigational compound/compound class being used in the study
  9. A positive Hepatitis B surface antigen (HBsAg) or positive HCV antibody
  10. History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations
  11. History of liver disease, such as cirrhosis or chronic active hepatitis B and C.
  12. Known gallbladder or bile duct disease, acute or chronic pancreatitis
  13. Baseline ALT or AST > ULN
  14. Baseline total bilirubin > 1.5x ULN
  15. Subjects on dialysis
  16. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 5 times the terminal half-life of study treatment (6 days). Highly effective contraception methods include:

    • Total abstinence or
    • Male or female sterilization or
    • Combination of any two of the following (a+b or a+c, or b+c):

      • Use of oral, injected or implanted hormonal methods of contraception
      • Placement of an intrauterine device (IUD) or intrauterine system (IUS)
      • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
  17. Sexually active males unless they use a condom during intercourse while taking drug and for 5 half-lives (6 days) after stopping SOM230 medication and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
  18. Potentially unreliable or vulnerable subjects (e.g. person kept in detention) and those judged by the investigator to be unsuitable for the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01578928

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Locations
Germany
Novartis Investigative Site Recruiting
Berlin, Germany, 14050
Novartis Investigative Site Completed
Berlin, Germany, 14050
South Africa
Novartis Investigative Site Not yet recruiting
Bloemfontein, Free State, South Africa, 9300
Novartis Investigative Site Recruiting
Bloemfontein, Free State, South Africa, 9300
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01578928     History of Changes
Other Study ID Numbers: CSOM230B2126, 2011-005922-23
Study First Received: April 12, 2012
Last Updated: May 19, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
South Africa: Department of Health

Keywords provided by Novartis:
renal, impairment, endstage renal disease
renal
impairment
endstage renal disease

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on August 28, 2014