Wirelessly Observed Therapy in Comparison to Directly Observed Therapy for the Treatment of Tuberculosis

PHARMACOKINETIC (PK) SUBSTUDY

The purpose of the PK substudy is to prospectively evaluate the pharmacokinetic parameters of isoniazid (INH) and rifampin (RIF) concentrations derived from dosing with Rifamate when given in native format compared to over encapsulated, ingestion sensor-enabled format.

The UCSD substudy aims to co-enroll 12 patients with Phase 1- the two-week investigation period of the characteristics of use of DHFS and patient acceptability. These subjects will be randomized to start on either Phase 1 or on two weeks of native Rifamate followed by 24-hour PK sampling.

Inclusion criteria

• Basic competency in understanding written and verbal information as it applies to DHFS use.
• Persons undergoing treatment for TB that includes at least isoniazid and rifampin at the time of entry to Phase 1; of note, patients must be sputum smear negative at the time of study entry.
• Laboratory values obtained by screening laboratories within 30 days of entry:

• Absolute neutrophil count (ANC) >= 1,000/mm3.
• Hemoglobin >= 9.0 g/dL.
• Platelet count >= 75,000/mm3.
• AST (SGOT), ALT (SGPT), and alkaline phosphatase <= 3 x ULN.
• Total bilirubin <= 1.5 x ULN and direct bilirubin.
• Females of childbearing potential must agree to use contraception throughout the study period.
• Men and women age >= 18 years.
• Eligible for anti-mycobacterial medications and in possession of prescriptions for isoniazid and rifampin, or Rifamate, as appropriate.
• Willing to follow all protocol requirements.
• Ability to use mobile device per investigator determination, and to wear PDH wearable sensor (i.e., no skin conditions precluding use).
• Ability and willingness of subjects to give written informed consent.

Exclusion criteria

• Female who is pregnant or breast-feeding, or of childbearing potential and has a tuberculin positive test at screening and disagrees to use contraception throughout the study period.
• Use of any of the prohibited medications or other non-informed medications within 30 days of study entry.
• Known hypersensitivity to any of the study drugs.
• Known sensitivity to skin adhesives.
• Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 30 days prior to study entry (Day 0).
• Evidence of any anti-mycobacterial resistance, clinical or genetic, prior to study entry. Resistance testing results must be available for review by the site investigator and study protocol team prior to enrollment to ensure that no exclusionary resistance exists.
• Active drug or alcohol use, or dependence, or other conditions that, in the opinion of the site investigator, would interfere with adherence to study requirements.