Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Subcutaneous Administration of Lisofylline to Healthy Normal Subjects and Subjects With Type 1 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
DiaKine Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00896077
First received: May 7, 2009
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

Type 1 diabetes mellitus (T1DM) is an autoimmune disease. Autoimmune diseases happen when the immune system does not identify part of the body as belonging to it. The immune system then destroys that part as if it were an unknown tissue in the body. In T1DM, the body kills the cells in the pancreas that produce insulin. Insulin is the hormone that "unlocks" the cells of the body. It allows glucose to enter and fuel them. Special cells in the body called islets make the insulin. Since glucose cannot enter the cells, it builds up in the blood. The body's cells literally starve to death. Children are at risk of developing T1DM and the risk is much higher than other severe, chronic childhood diseases. The only treatments are a careful diet, planned physical activity, and testing blood sugar levels several times a day. The patient must also inject insulin each day or use an insulin pump. There is no cure for T1DM. Insulin injections are considered life support, because going without insulin for just a few days causes the blood to have too much acid in it and that can lead to death. On the other hand, taking too much insulin makes blood sugar levels go too low, and if untreated, can lead to death as well.

DiaKine is developing Lisofylline to treat the failed immune system. This is what caused T1DM in the first place and it does not go away. The purpose of this study is to see how safe the study drug is. The study is also going to compare the levels of study drug in the blood and to measure the effect of the study drug on other substances in the blood that are linked to type 1 diabetes. These levels will be measured after the study drug is given as an injection under the skin and an injection into the vein. To date, Lisofylline has been tested when given as an injection in the vein.

The investigators hypothesize that Lisofylline will be safe when given as an injection under the skin and in the vein and that levels of study drug will be very similar when given as an injection under the skin and in the vein.

The investigators also hypothesize that Lisofylline will have a positive effect on the substances in the blood that are linked to type 1 diabetes.


Condition Intervention Phase
Healthy
Type 1 Diabetes
Drug: Lisofylline
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Safety, Tolerability and Bioavailability Study of Lisofylline After Continuous Subcutaneous (12 mg/kg) and Intravenous (12 mg/kg) Administration in Healthy Subjects and in Subjects With Type 1 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by DiaKine Therapeutics, Inc.:

Primary Outcome Measures:
  • Safety (based on AEs, vital signs assessments, resting 12-lead ECG evaluations, physical examination findings and clinical laboratory test results) [ Time Frame: LSF Plasma levels: D1-2, 7-8; T 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24 h; D2, 8; T 5, 10, 15, 30 min and 1, 2, 3, 4, 6, 8, 10, 12, 16 h post inf. Cytokine, chemokine, insulin, free fatty acid STAT4 phosphorylation in monocytes: D1-2, 7-8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic (PK) parameters will include AUC0-t, AUC0-inf, Cmax, Tmax, t1/2, kel, CL, Vdss and F [ Time Frame: LSF Plasma levels: D1-2, 7-8; T 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24 h; D2, 8; T 5, 10, 15, 30 min and 1, 2, 3, 4, 6, 8, 10, 12, 16 h post inf. Cytokine, chemokine, insulin, free fatty acid STAT4 phosphorylation in monocytes: D1-2, 7-8 ] [ Designated as safety issue: No ]
  • Pharmacodynamic (PD) assessments (blood will be collected for determination of serum cytokine, chemokine, insulin and FFA levels at time points noted previously) [ Time Frame: LSF Plasma levels: D1-2, 7-8; T 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24 h; D2, 8; T 5, 10, 15, 30 min and 1, 2, 3, 4, 6, 8, 10, 12, 16 h post inf. Cytokine, chemokine, insulin, free fatty acid STAT4 phosphorylation in monocytes: D1-2, 7-8 ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: May 2009
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Subcutaneous
Subcutaneous administration of LSF
Drug: Lisofylline
Lisofylline via i.v. administration vs Lisofylline vs s.c. administration
Active Comparator: IV
IV administration arm
Drug: Lisofylline
Lisofylline via i.v. administration vs Lisofylline vs s.c. administration

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who meet all of the following criteria are eligible for participation in the healthy subject cohort of the study:

    1. Ability to understand and provide written informed consent;
    2. Ability to complete the study in compliance with the protocol;
    3. Healthy male or female between 18 and 45 years of age, inclusive;
    4. Female subjects must be non-pregnant and non-lactating and must be surgically sterile, postmenopausal, or willing to use adequate contraception, including but not limited to hormonal contraceptive, diaphragm, condom or intrauterine device, during the course of the study. Female subjects must agree not to attempt to become pregnant during the study;
    5. Male subjects must be willing to use effective birth control if their female partners are of child-bearing potential starting the day prior to the first dose of study drug until the end of the study;
    6. Weigh at least 50 kg (110 lbs);
    7. Body mass Index (BMI) between 19 and 34.5 kg/m2, inclusive;
    8. No clinically significant abnormal findings on the physical examination, medical history, vital signs assessment, resting 12-lead ECG evaluation or clinical laboratory test results during screening;
    9. A negative hepatitis B surface antigen, hepatitis C antibody or HIV antibody test result at screening or within the previous 3 months.
  • Subjects who meet all of the following criteria are eligible for participation in the type 1 DM cohort of the study:

    1. Ability to understand and provide written informed consent;
    2. Ability to complete the study in compliance with the protocol;
    3. Male or female between 18 and 45 years of age, inclusive;
    4. If the subject is female, she must be non-pregnant and non-lactating and must be surgically sterile, postmenopausal, or willing to use adequate contraception, including but not limited to hormonal contraceptive, diaphragm, condom or intrauterine device, during the course of the study. Female subjects must agree not to attempt to become pregnant during the study;
    5. Male subjects must be willing to use effective birth control if their female partners are of child-bearing potential starting the day prior to administration of the first dose of study drug until the end of the study;
    6. Weigh at least 50 kg (110 lbs);
    7. Body Mass Index (BMI) between 19 and 34.5 kg/m2, inclusive;
    8. Clinical diagnosis of type 1 DM at least 2 years prior to screening;
    9. Treatment with insulin for at least 1 year and on a stable dose for at least 3 months prior to screening. Dose must be ≤ 0.8 units/kg/day;
    10. Currently self-monitoring blood glucose levels at least daily;
    11. HbA1c level 6-10%, inclusive;
    12. Serum C-peptide level ≤ 0.6 ng/mL;
    13. Serum creatinine < 1.5 mg/dL for males, and <1.4 mg/dL for females;

Exclusion Criteria:

  • Subjects meeting any of the following criteria will be excluded from participation in the healthy subject cohort of the study:

    1. A clinically significant laboratory abnormality or other clinical findings indicative of a clinically significant exclusionary disease (including but not limited to renal, hepatic, gastrointestinal, cardiovascular, neurological disease);
    2. History of any significant drug allergy;
    3. History of difficulty with phlebotomy;
    4. Use of any recreational drugs within the past year or a previous history of drug or alcohol abuse;
    5. Positive results from a urine screen for alcohol or substances of abuse at screening or upon admission to the Clinic;
    6. Current smoker or user of any tobacco products;
    7. Use of any prescription drug therapy within 14 days prior to receiving study drug;
    8. Use of any over-the-counter (OTC) drugs or herbal preparations within 72 hours prior to receiving study drug;
    9. Consumption of any caffeine-containing foods or beverages within 24 hours prior to receiving study drug;
    10. Consumption of alcohol within 24 hours prior to admission to the Clinic;
    11. Consumption of any grapefruit or grapefruit-containing juices within 72 hours prior to receiving study drug;
    12. Use of an investigational drug or product, or participation in a drug research study within 30 days prior to receiving drug;
    13. Prior exposure to lisofylline;
    14. The donation of blood (1 pint or more) within 30 days or plasma within 7 days of receiving study drug;
    15. Any condition which in the opinion of Investigator would interfere with the participant's ability to provide informed consent, comply with study instructions, possibly confound interpretation of study results, or endanger the participant if he or she took part in the trial
  • Subjects meeting any of the following criteria will be excluded from participation in the type 1 DM cohort of the study:

    1. Known or suspected history of significant gastrointestinal, liver or cardiac disease, including stroke, peripheral vascular disease or any related symptom
    2. History of peptic ulcer disease and or gastrointestinal bleeding/perforation;
    3. History or presence of proliferative retinopathy, severe non-proliferative retinopathy, macular edema or presence of untreated diabetic eye disease;
    4. History of treated peripheral or autonomic neuropathy;
    5. History of hypoglycemia unawareness, and/or episodes of severe hypoglycemia within 60 days prior to screening;
    6. Non-healed diabetic ulcer;
    7. Diagnosis of type 2 DM, based upon subject report;
    8. Use of oral antihyperglycemic agents, pentoxifylline and/or theophylline;
    9. Use of any drug therapy that directly affects gastrointestinal motility;
    10. History of any significant drug allergy;
    11. History of difficulty with phlebotomy;
    12. Use of any recreational drugs within the past year or a previous history of drug or alcohol abuse;
    13. Positive results from a urine screen for alcohol or substances of abuse at screening or upon admission to the Clinic;
    14. Current smoker or user of any tobacco products;
    15. Use of any prescription drug therapy within 14 days prior to receiving study drug, with the exception of therapy to treat DM;
    16. Use of any over-the-counter (OTC) drugs or herbal preparations within 72 hours prior to receiving study drug;
    17. Consumption of any caffeine-containing foods or beverages within 24 hours prior to receiving study drug;
    18. Consumption of alcohol within 24 hours prior to admission to the Clinic;
    19. Consumption of any grapefruit or grapefruit-containing juices within 72 hours prior to receiving study drug;
    20. Use of an investigational drug or product, or participation in a drug research study within 30 days prior to receiving drug;
    21. Prior exposure to lisofylline;
    22. The donation of blood (1 pint or more) within 30 days or plasma within 7 days of receiving study drug;
    23. Any condition which in the opinion of Investigator would interfere with the participant's ability to provide informed consent, comply with study instructions, possibly confound interpretation of study results, or endanger the participant if he or she took part in the trial
  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: NCT00896077

Locations
United States, New Jersey
Advanced Biomedical Research, Inc. (ABR)
Hackensack, New Jersey, United States, 07601
Sponsors and Collaborators
DiaKine Therapeutics, Inc.
  More Information

No publications provided

Responsible Party: DiaKine Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT00896077     History of Changes
Other Study ID Numbers: DT-002
Study First Received: May 7, 2009
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by DiaKine Therapeutics, Inc.:
healthy subjects

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Lisofylline
Adjuvants, Immunologic
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Central Nervous System Agents
Immunologic Factors
Immunosuppressive Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014