Patient case: 58-year-old female with Lung cancer. Genetic variant: NTRK1. Other conditions: Depression, Hypertension, Diabetes.

Clinical trial: MAD Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PB-119 to Subjects With T2DM

Summary: This was a phase 1, randomized, double-blind, placebo-controlled, sequential parallel group, MAD study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of four once-weekly subcutaneous doses of PB-119 to subjects with T2DM.

Detailed description: Dose levels of 25 µg, 50 µg, 100 µg and 200 µg with a dosing regimen of once weekly for 4 consecutive weeks will be evaluated

Eligibility: Inclusion Criteria:
  1. Patients in whom T2DM has been diagnosed for at least 3 months prior to screening and have not been taking any treatment but have made lifestyle modifications (i.e., diet and exercise) for at least 4 weeks or are taking metformin (with no change in the treatment including dose over the past 2 months).
  2. In good general health as determined by the investigator at screening evaluation
  3. Male and/or female subjects between the ages of 18 and 70 years, inclusive;
  4. Are capable of giving informed consent and complying with study procedures;
  5. Body Mass Index (BMI) of approximately 22 to 40 kg/m2;
  6. Fasting C-peptide test result must be >0.4 nmol/L;
  7. HbA1c ≥6.5 % and ≤12%;
  8. Female subjects must have a negative urine pregnancy test result prior to enrollment.
  9. Nonsmoker,
  10. Willing and able to adhere to study restrictions and to be confined at the clinical research center.
  Exclusion Criteria:
  1. Subjects with a personal or family history of medullary thyroid carcinoma (MTC) or in subjects with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2);
  2. Screening fasting blood glucose ≤100 or ≥270 mg/dL
  3. Type 1 diabetes mellitus, or latent autoimmune diabetes in adults; diabetic neuropathy, retinopathy or nephropathy;
  4. Previous treatment with an approved or investigational GLP-1 mimetic;
  5. Patients treated with any investigational drugs within 6 weeks of screening;
  6. Subjects with pancreatitis;
  7. Clinically significant gastrointestinal disorder
  8. History or symptoms of clinically significant cardiovascular disease, particularly coronary artery disease, arrhythmias, atrial tachycardia,
  9. Uncontrolled hypertension at screening;
  10. History of clinically significant central nervous system disease including: transient ischemic attack, stroke, seizure disorder, depression,
  11. History of liver disease
  12. History of clinically significant renal disease
  13. Uncontrolled severe dyslipidemia;
  14. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody;
  15. A hospital admission or major surgery within 30 days prior to screening;
  16. A history of prescription drug abuse, or illicit drug use within 6 months prior to screening;
  17. A history of alcohol abuse according to medical history within 6 months prior to screening;
  18. A positive screen for alcohol, or drugs of abuse;
  19. An unwillingness or inability to comply with food and beverage restrictions during study participation;
  20. Use of prescription or over-the-counter (OTC) medications, and herbal An
  21. Unwillingness of male participants to use appropriate contraceptive measures if engaging in sexual intercourse with a female partner of childbearing potential. Appropriate measures include use of a condom and spermicide and, for female partners, use of an intrauterine device (IUD), diaphragm with spermicide, oral contraceptives, injectable progesterone, progesterone subdermal implants, or a tubal ligation. Sexual intercourse with pregnant or lactating women is prohibited

Relevance to patient case: not relevant