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The Effect Of NS-0200 and NS-0300 Versus Placebo on Weight In Obesity

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.
ClinicalTrials.gov Identifier: NCT03364335
Recruitment Status : Completed
First Posted : December 6, 2017
Results First Posted : November 27, 2018
Last Update Posted : December 18, 2018
Sponsor:
Information provided by (Responsible Party):
NuSirt Biopharma

Brief Summary:
This is a 24-week study to evaluate the effects of two fixed-dose combinations of leucine and sildenafil or two fixed-dose combinations of leucine, sildenafil and metformin compared to placebo. The primary objective of this study is to evaluate the percentage change in body weight in subjects from Baseline/Visit 2 (Day 1) to Study Termination/Visit 8 (Day 168/Week 24).

Condition or disease Intervention/treatment Phase
Obesity Drug: Leu Sil 1.0mg Drug: Leu Sil 4.0mg Drug: Leu Met Sil 1.0mg Drug: Leu Met Sil 4.0mg Drug: Placebo Phase 2

Detailed Description:

This is a randomized, 24-week, placebo-controlled, double-blind study to evaluate the effects of two fixed-dose combinations of leucine and sildenafil or two fixed-dose combinations of leucine, sildenafil and metformin compared to placebo. Subjects meeting all the inclusion criteria and no exclusion criteria will be randomized to one of five study arms.

The primary objective of this study is to evaluate the percentage change in body weight in subjects from Baseline/Visit 2 (Day 1) to Study Termination/Visit 8 (Day 168/Week 24) receiving two fixed-dose combinations of leucine and sildenafil or two fixed-dose combinations of leucine, sildenafil and metformin compared to placebo. Secondary objectives will also assess changes in absolute body weight, percentage of patients with ≥5% body weight loss, change in waist circumference, change in HbA1c, change in fasting glucose, change in blood lipids such as cholesterol, LDL, HDL, triglycerides, change in blood pressure and changes in in C-reactive protein. In addition this study will evaluate the safety and tolerability of NS-0200 and NS-0300.

Patients will have one screening visits which will determine their eligibility based on lab tests. Once qualified, patients will be randomly assigned to either one of the treatment groups or the placebo control group and monitored for a total of 24 weeks. Patients will return to the clinic each month for lab tests, and routine examinations.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 267 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: This is a double blind, placebo controlled trial
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Study of Effects of Two Fixed-dose Leucine-sildenafil Combinations (NS-0300) or Two Fixed-dose Leucine-sildenafil-metformin Combinations (NS-0200) Versus Placebo on Body Weight in Obesity
Actual Study Start Date : January 8, 2018
Actual Primary Completion Date : August 6, 2018
Actual Study Completion Date : August 17, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Body Weight

Arm Intervention/treatment
Placebo Comparator: Placebo
Each dose of placebo will consist of three tablets, identical in appearance to those used in the two active treatment arms, containing 93.5% Microcrystalline cellulose PH 102, 5.0% Crospovidone XL 10, 1.0% Silica gel (Syloid 244), 0.5% Magnesium stearate I MF3V for the leucine matched placebo and 99.5% Avicel PH200 , 0.5% magnesium stearate (w/w) and Opadry II White coating 3% weight gain for the sildenafil matched placebo.
Drug: Placebo
Placebo

Experimental: Leu Sil 1.0mg
3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 1.0 mg of sildenafil
Drug: Leu Sil 1.0mg
Leu 1100 mg + 1mg Sil BID
Other Name: NS-0300-1.0

Drug: Leu Sil 4.0mg
Leu 1100 mg + 4mg Sil BID
Other Name: NS-0300-4.0

Experimental: Leu Sil 4.0mg
3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 4.0 mg of sildenafil
Drug: Leu Sil 1.0mg
Leu 1100 mg + 1mg Sil BID
Other Name: NS-0300-1.0

Drug: Leu Met Sil 1.0mg
Leu 1100 mg + Met 500mg + 1mg Sil BID
Other Name: NS-0200-1.0

Experimental: Leu Met Sil 1.0mg
3 capsules BID consisting of 2 capsules containing 550 mg L-leucine and 250 mg metformin and 1 capsule containing 1.0 mg of sildenafil
Drug: Leu Sil 1.0mg
Leu 1100 mg + 1mg Sil BID
Other Name: NS-0300-1.0

Drug: Leu Sil 4.0mg
Leu 1100 mg + 4mg Sil BID
Other Name: NS-0300-4.0

Drug: Leu Met Sil 4.0mg
Leu 1100 mg + Met 500mg + 4mg Sil BID
Other Name: NS-0200-4.0

Experimental: Leu Met Sil 4.0mg
3 capsules BID consisting of 2 capsules containing 550 mg L-leucine and 250 mg metformin and 1 capsule containing 4.0 mg of sildenafil
Drug: Leu Sil 1.0mg
Leu 1100 mg + 1mg Sil BID
Other Name: NS-0300-1.0

Drug: Leu Met Sil 1.0mg
Leu 1100 mg + Met 500mg + 1mg Sil BID
Other Name: NS-0200-1.0

Drug: Leu Met Sil 4.0mg
Leu 1100 mg + Met 500mg + 4mg Sil BID
Other Name: NS-0200-4.0




Primary Outcome Measures :
  1. Percentage Body Weight Change [ Time Frame: Baseline to Day 168 ]
    The percentage body weight change from baseline to Day 168 was evaluated.


Secondary Outcome Measures :
  1. Change in Absolute Body Weight [ Time Frame: Baseline to Day 168 ]
    The change in absolute body weight from baseline to day 168 was evaluated.

  2. Change in Percentage of Patients With ≥5% Body Weight Loss [ Time Frame: Baseline to Day 168 ]
    The number of patients with ≥5% body weight loss in each group was assessed from baseline to day 168.

  3. Change in Waist Circumference [ Time Frame: Baseline to Day 168 ]
    The change in waist circumference by using a tape measure across the mid-section was evaluated in subjects from baseline to day 168.

  4. Change in Total Cholesterol [ Time Frame: Baseline to Day 168 ]
    Changes in total cholesterol was examined by standard blood chemistry.

  5. Change in HDL Cholesterol [ Time Frame: Baseline, Day 168 ]
    Changes were measured in HDL cholesterol from Baseline to day 168 by standard blood chemistry.

  6. Change in LDL Cholesterol [ Time Frame: Baseline, 168 days ]
    Changes in LDL Cholesterol was measured by standard blood chemistry from baseline to day 168.

  7. Change in Triglycerides [ Time Frame: Baseline, Day 168 ]
    The change in triglycerides was evaluated by standard blood chemistry in subjects from Baseline to Day 168.

  8. Change in Plasma Glucose [ Time Frame: Baseline to Day 168 ]
    Change in plasma glucose was examined through standard fasting blood chemistry.

  9. Change in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, Day 168 ]
    Change in Hemoglobin A1c was assessed in the subjects from baseline to day 168.

  10. Change in Diastolic Blood Pressure [ Time Frame: Baseline to Day 168 ]
    Diastolic blood pressure was measured by standard blood pressure monitor.

  11. Change in Systolic Blood Pressure [ Time Frame: Baseline, Day 168 ]
    Change in Systolic blood pressure was assessed in patients from baseline to Day 168

  12. Change in Inflammatory Markers [ Time Frame: Baseline to Day 168 ]
    hs-C-Reactive Protein (CRP) levels was examined by standard blood chemistry.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Maximum of 70% female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥18 and ≤65 at study entry.
  2. Is male, or female and, if female, meets all of the following criteria:

    1. Not breastfeeding
    2. Post-menopausal or negative serum pregnancy test result (human chorionic gonadotropin, beta subunit [β-hCG]) at Screening/Visit 1 (Day-7/Week-1) (not required for hysterectomized females)
    3. If of childbearing potential (including peri-menopausal women who have had a menstrual period within one year) must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as double barrier methods [male condom with spermicide, with or without cervical cap or diaphragm], implants, injectables, oral contraceptives [must have been using for at least the last 3 months], some intrauterine contraceptive devices, tubal ligation, or in an established relationship with a vasectomized or same sex partner) during the entire duration of the study
  3. Stable body weight (±5%) and health over the last 3 months.
  4. Has a BMI between 30 kg/m2 and 45 kg/m2
  5. Stable diet within the last three months
  6. Subjects on antidepressants, excluding those listed in the exclusion criteria, must have been on a stable dose regiment for at least 3 months prior to study enrollment and maintain stable dose during the study
  7. Clinical laboratory tests (hematology, clinical chemistry, and urinalysis) either normal, not clinically significant or with abnormalities consistent with obesity
  8. Is able to read, understand, and sign the informed consent forms (ICF) and, when applicable, an authorization to use and disclose protected health information form (consistent with Health Insurance Portability and Accountability Act of 1996 [HIPAA] legislation), communicate with the investigator, and understand and comply with protocol requirements.

Exclusion Criteria:

  1. Diagnosis of diabetes or on a diabetes medication
  2. HbA1c ≥6.5% at Screening/Visit 1 (Day-7/Week-1)
  3. Severe renal impairment (eGFR < 45 mg/mL/1.73 m2) and/or patients with acute or chronic metabolic acidosis. Acidosis is defined as >25mmol/L computed without K.

    Normal is 8- 16, but acidosis is >25

  4. Use of any of the following medications in the eight weeks prior to entering screening for study participation and during the study:

    1. Use of any anti-diabetes medication including metformin and any combination drug that contains metformin
    2. Sildenafil
    3. Tadalafil
    4. Vardenafil
    5. OCT2/MATE inhibitors (e.g. cimetidine, quinidine, and pyrimethamine)
    6. Riociguat (guanylate cyclase stimulant)
    7. Alpha blockers
    8. Nitrates (e.g. oral nitrates, sublingual nitroglycerine and nitroglycerine patches)
    9. Potent CYP3A4 inhibitors (e.g. clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir)
    10. All antihypertensive medications
    11. Medications associated with weight changes

      • Drugs approved for the treatment of obesity
      • Cypropheptadine or medroxyprogesterone
      • Atypical anti-psychotic drugs
      • Tricyclic antidepressants
      • Lithium, MAO's, glucocorticoids
      • SSRI's or SNRI's
      • Antiepileptic drugs
      • Systemic corticosteroids
      • Stimulants e.g. amphetamines
    12. Any dietary supplement that is labeled for weight management or maintenance of healthy weight
  5. Diagnosis or evidence of eating disorders
  6. ≥ 5% weight change in the last 3 months
  7. Subjects who have had bariatric surgery
  8. An infection requiring antibiotic treatment within the last 30 days
  9. Any chronic inflammatory disease, e.g. inflammatory bowel disease rheumatoid arthritis, vasculitis, systemic lupus erythematosus
  10. Diseases interfering with metabolism (including metabolism of branched chain amino acids) and/or ingestive behavior (myxedema, Cushing's disease, diabetes, schizophrenia, major psychoses, maple syrup urine disease, unmanaged depression etc.)
  11. History of alcohol abuse (defined ≥ 21 drinks per week for males and > 14 drinks per week for females), within the past 3 months or failure on urinary drug screen
  12. History of substance abuse (including alcohol abuse as defined above) in the past 12 months or a positive screen for drugs (opioids without a prescription), including marijuana, of abuse or alcohol at screening.
  13. Has received any investigational drug within 3 months of Screening.
  14. Has donated blood within 3 months before Screening or is planning to donate blood during the study (due to HbA1c reading at screening)
  15. Other medical conditions that may diminish life expectancy to <2 years, including known cancers
  16. Have been diagnosed with metastatic carcinomas in the last 5 years
  17. Has known allergies or hypersensitivity to metformin, sildenafil or leucine
  18. Have suffered myocardial infarction, stroke, arrhythmia in the last 6 months
  19. Resting hypotension (BP <90/50 mmHg) or severe hypertension (BP >170/110 mmHg) If both or one of the parameters for diastolic or systolic BP is meet
  20. Cardiac failure or coronary artery disease causing unstable angina
  21. History or evidence at screening of left ventricular outflow obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic control of blood pressure
  22. At risk for priapism due to anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, Peyronie's disease) or other conditions that predispose to priapism (e.g., sickle cell anemia, multiple myeloma, or leukemia)
  23. Clinical evidence of hepatic impairment and/or ALT/AST >5X ULN
  24. Is an immediate family member (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at the clinical study site, or NuSirt Biopharma.
  25. Is employed by NuSirt Biopharma (defined as an employee, temporary contract worker, or designee responsible for the conduct of 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 ClinicalTrials.gov identifier (NCT number): NCT03364335


Locations
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United States, Alabama
AMR
Mobile, Alabama, United States, 36608
United States, California
Catalina Research Institute
Montclair, California, United States, 91763
Northern California Research
Sacramento, California, United States, 95821
United States, Idaho
ACR
Meridian, Idaho, United States, 83642
United States, Illinois
Synexus
Chicago, Illinois, United States, 60602
United States, Louisiana
Pennington Biomedical Research Center
Baton Rouge, Louisiana, United States, 70808
Clinical Trials Management
Metairie, Louisiana, United States, 70006
United States, Missouri
Synexus
Saint Louis, Missouri, United States, 63141
United States, Nevada
AMR
Las Vegas, Nevada, United States, 89119
United States, Ohio
Rapid Medical Research
Cleveland, Ohio, United States, 44122
United States, South Carolina
Medical Research South
Charleston, South Carolina, United States, 29407
United States, Tennessee
Premier
Clarksville, Tennessee, United States, 37040
United States, Texas
Synexus
Dallas, Texas, United States, 75234
Synexus
San Antonio, Texas, United States, 78229
United States, Utah
ACR
Jordan, Utah, United States, 84088
Sponsors and Collaborators
NuSirt Biopharma
Investigators
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Study Chair: Michael B Zemel, PhD NuSirt Biopharma
  Study Documents (Full-Text)

Documents provided by NuSirt Biopharma:
Study Protocol  [PDF] December 4, 2017
Statistical Analysis Plan  [PDF] December 4, 2017


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Responsible Party: NuSirt Biopharma
ClinicalTrials.gov Identifier: NCT03364335     History of Changes
Other Study ID Numbers: NS-WM-01
First Posted: December 6, 2017    Key Record Dates
Results First Posted: November 27, 2018
Last Update Posted: December 18, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Metformin
Sildenafil Citrate
Hypoglycemic Agents
Physiological Effects of Drugs
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents