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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01578928
Recruitment Status : Completed
First Posted : April 17, 2012
Last Update Posted : March 3, 2015
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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 or disease Intervention/treatment Phase
Renal Impairment Drug: SOM230 Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : May 2012
Actual Primary Completion Date : May 2014
Actual Study Completion Date : May 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Pasireotide

Arm Intervention/treatment
Experimental: SOM230
subjects with varying degrees of renal impairment along with subjects without renal impairment
Drug: SOM230

Primary Outcome Measures :
  1. 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 ]
    Description: Cmax, AUCinf, AUClast, CL/F, CLR, glucose, insulin, glucagon

Secondary Outcome Measures :
  1. 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 ]
    Description: Vz/F, T1/2, Fu, Cmax,u, AUCinf,u, AUClast,u, CLu/F and Vu/F

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01578928

Novartis Investigative Site
Berlin, Germany, 14050
South Africa
Novartis Investigative Site
Bloemfontein, Free State, South Africa, 9300
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals Identifier: NCT01578928     History of Changes
Other Study ID Numbers: CSOM230B2126
2011-005922-23 ( EudraCT Number )
First Posted: April 17, 2012    Key Record Dates
Last Update Posted: March 3, 2015
Last Verified: March 2015

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
renal, impairment, endstage renal disease
endstage renal disease

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs