A Clinical Trial of the Safety, Pharmacokinetics and Hematologic Effects of Imatinib on Myelopoiesis in Adults When Given With and Without Isoniazid and Rifabutin (IMPACT-TB)

This is an interventional treatment trial for Tuberculosis focused on measuring Imatinib, Rifabutin, Isoniazid Read More

Inclusion Criteria:

• Adult age between 18 years and 55 years
• Body mass index (BMI) greater than 18.5 kg/m^2
• At least 8 years formal education, with appropriate reading and comprehension skills
• Able and willing to provide written informed consent
• Males must agree to using contraception during the study and for 2 weeks after the last dose of study drug.

• If a female participant is of reproductive potential, the participant (and her partner) must agree to use of one of the following combinations of birth control during the study and for 2 weeks after the last dose of study drug (or tubal ligation as a single method):

  • Use of a double-barrier method of contraception: condoms (male or female) and a diaphragm or cervical cap with spermicide;
  • Use of an intrauterine device (IUD) and a barrier method: condoms (male or female, with or without spermicide) or a diaphragm or cervical cap with spermicide;
  • Tubal ligation.
  • Important Note: Due to documented effects of rifabutin on effectiveness of hormonal contraceptives (16-18), these are not included as options here with the exception of an IUD. Women who are post-menopausal, defined as age greater than 45 and no menses for at least 1 year, or who have had a hysterectomy, are considered not of reproductive potential.

Exclusion Criteria:

• Current or imminent treatment for significant infection
• Pregnant or breastfeeding
• HIV positive status as determined by a U.S. Food and Drug Administration (FDA)-approved HIV assay
• Hepatitis B infection, as determined by an FDA-approved hepatitis B surface antigen assay
• Hepatitis C infection, as determined by an FDA-approved positive Hepatitis C antibody assay
• Known infection with Mycobacterium tuberculosis (MTB)
• History of allergy or hypersensitivity to imatinib, isoniazid or rifabutin.
• History of enrollment in other clinical trials with investigational agents within 8 weeks
• Cardiac arrhythmia requiring medication, or any clinically significant electrocardiogram (ECG) abnormality
• Exam consistent with congestive heart failure (e.g., edema)
• Random blood glucose greater than 140 mg/dL or history of unstable diabetes mellitus requiring hospitalization for hyper or hypoglycemia within the past year prior to start of screening
• Use of systemic corticosteroids within the past 28 days

• Any of the following readings from a complete blood count that fall outside the normal ranges as listed here (Emory Medical Lab Reference Ranges, 2019, with some variation for different ethnic groups incorporated in the system):

  • White blood cell count: Female- 4.0-10.0 10E3/mcL, Male- 4.2-9.1 10E3/mcL
  • Hemoglobin: Female-11.4-14.4 gm/dL, Male-12.9-16.1 gm/dL
  • Platelet count: Female-150-400 10E3/mcL, Male-150-400 10E3/mcL
  • Absolute neutrophil count: Female- 0.91-5.53 10E3/mcL, Male- 0.67-6.4110E3/mcL
  • Absolute lymphocyte count: Female- 0.65-3.05 10E3/mcL, Male- 0.72-3.29 10E3/mcL

• Any of the following chemistry panel and liver function test readings that fall outside the normal ranges as listed here (Emory Medical Lab Reference Ranges, 2019):

  • Serum potassium: Female- 3.5-5.1 mmol/L, Male- 3.5-5.1 mmol/L
  • Alkaline phosphatase (ALP): Female- 34-104unit/L, Male- 34-104unit/L
  • Alanine aminotransferase (ALT): Female- 7-52 unit/L, Male-7-52 unit/L
  • Aspartate aminotransferase (AST): Female-13-39 unit/L, Male-13-39 unit/L
  • Gamma-glutamyl transferase (GGT): Female- 9-64 unit/L, Male- 9-64 unit/L
  • Total Bilirubin: Female- 0.3-1.0 mg/dL, Male- 0.3-1.0 mg/dL
  • Creatinine: Female- 0.60-1.20 mg/dL, Male- 0.7-1.3mg/dL
• Cirrhosis of the liver, or any known active or chronic liver disease
• Current or past alcohol or elicit/recreational drug use, which in the expert judgment of the Investigator, will interfere with the participant's ability to comply with the protocol requirements.
• Any experimental medications for less than 8 weeks prior to screening or anticipated use during the trial
• Current (within 30 days prior to the first dose of study drug) or anticipated use of antimetabolites; alkylating agents; or other drugs or herbal preparations (including St. John's wort), known to affect activity of the CYP3A4 enzyme pathway
• Consumption of grapefruit, grapefruit juice, or grapefruit-related citrus fruits (e.g., pomelos) within 7 days before assessment for eligibility
• Unwilling to avoid grapefruit or grapefruit-related citrus fruits/pomelo during the course of the study
• Unwilling to avoid alcohol for the duration of the study
• Unwilling to abstain from taking acetaminophen-containing medications during the 28-day study drug dosing period, due to increased risk of liver toxicity
• History of major medical disorders including metabolic, endocrine, hypothyroid, hepatic, renal, hematologic, pulmonary, gastrointestinal, autoimmune or cardiovascular disorders
• Uncontrolled hypertension (persistent measurements at or above 150/100)
• Participants who are, in the opinion of the Investigator, unable to comply with the dosing schedule and protocol evaluations
• Diarrhea defined as 4 or more stools per day
• Active involvement (by the participant or the participant's partner) in In Vitro Fertilization or another assisted reproductive technology procedure
• Emory students currently enrolled in a course taught by the principal investigator (PI) or a Co-Investigator
• Emory employees currently working under supervision of the PI or a Co-Investigator