A guide to STREAM trial medicines: Know your medication!

Overview STREAM trial design and medicines Information for participants How to store trial medicine What to do with extra medicine How to take trial medicine Strategies for improving medication adherence Possible side effects and interactions of trial medicines

STREAM trial design and medicines

STREAM trial design Participants randomly assigned to 4 treatment groups or “arms” (A,B,C and D) Arm A => national guidelines for MDR-TB Arms B,C and D => different combinations of available MDR-TB medicines (oral and injectable) for 6 or 9 months Aim to evaluate the effectiveness of shorter treatment regimens for MDR-TB New medicine – Bedaquiline (Sirturo®) – added to some arms Bedaquiline is the first new medicine in over 50 years for the treatment of tuberculosis Approval from US Food and Drug Administration - December 2012 Conditional marketing authorization from European Medicines Agency - 2013

STREAM Trial Medicines

STREAM Trial Medicines Participants are randomly assigned to 4 different treatment groups (A,B,C and D) B,C and D use combinations of 6 or 7 different medicines in the intensive and continuation phases of treatment Bedaquiline is included in regimens C and D Varies by country B 40 weeks C 40 weeks D 28 weeks

STREAM Trial Medicines Depending on treatment group, participants may take up to 19 pills every day during the intensive and continuation phases of treatment. Participants in group B and D also have injections.

Information for participants

How to store trial medicines Properly storing trial medicines helps limit exposure to damaging effects and assure their integrity and quality Trial medicines should be stored safely and securely out of the sun, away from the sink/basin and hot appliances Trial medicines should be stored in a cool, dry place For example, medication should not be stored in the bathroom. Heat and moisture from the sink, bath and shower may damage tablets Be sure to store trial medicines so that insects and animals can’t reach them

How to store trial medicines Trial medicines should be stored out of reach of anyone other than the patient and his/her DOT supporter PLEASE, always store medicines away from children and teenagers to prevent accidents

What to do with extra medicine If a participant has extra pills (for example, due to missed doses), they must take the extra pills with them to their next doctor’s visit: Doctor can properly dispose of them Doctor can monitor adherence

How to take trial medicines Participants should take trial medicines only as directed by the STREAM trial team This will ensure participants complete the recommended course of treatment and achieve maximum benefit from participating in the trial Participants should continue to take trial medicines even when they feel better or notice their symptoms get better Participants should NOT stop taking trial medicines without first consulting the STREAM trial team

How to take trial medicines should be taken with food should be swallowed whole with water should not be chewed or crushed should not be shared with anyone

Strategies for improving adherence “Medicines don’t work in patients who don’t take them.” Dr. C. Everett Koop, MD, US Surgeon General (1982 -1989)

Factors that influence adherence Factors that could make it harder for participants to take their trial medicines properly include: Complexity of their treatment Side effects of treatment Not understanding their illness Not understanding how trial medicines should be taken Substance abuse Trouble in swallowing Language barriers Forgetfulness Religious or cultural beliefs

How to improve adherence A few things can be done to improve treatment adherence in STREAM participants STREAM trial staff should explain to participants: Why each trial medication is being used The potential benefits and side effects of the medicine The potential for the development of resistance if not all the medication is taken How to properly store medications What to expect upon completion of treatment How response to treatment is measured

How to improve adherence STREAM trial staff should identify patients who miss visits or don’t take their medicines early and respond quickly with supportive care Participants can develop ways to remember to attend their visits and take the right dosage of their medication at the right time – e.g. pill boxes; alarm clocks; calendars; enlist support from family, friends or caregivers; establish a routine, i.e. take meds before your daily morning coffee or breakfast

Side effects STREAM trial medicines have the potential to cause a variety of side effects and therefore STREAM trial staff will monitor participants carefully to identify side effects and respond to them Some of the tests participants will undergo to identify side effects include: Blood tests Hearing tests ECGs to measure heart rhythm Vision tests

Common side effects Nausea Vomiting Diarrhea Headaches Numbness and pins and needles in feet Tingling Joint Pains

Side Effects Participants should notify the STREAM trial team if they have new side effects or if their side effects continue or get worse If a patient has an allergic reaction, like rash, hives, itching, shortness of breath, wheezing, cough, swelling of the face lips, tongue, or throat, they should seek medical attention immediately Some side effects can be serious, e.g. hearing loss and kidney failure Other side effects may go away as the patient’s body adjusts to the medicine, e.g. nausea Participants should ask the STREAM trial team what to do if they vomit within 30 minutes of taking trial medicines

Drug interactions The STREAM trial team should ask about all non-trial medicines participants are taking including prescription medicines, over the counter and herbal medications Helps the trial team to mitigate and monitor for drug interactions Participants should not take over-the-counter medications, herbals, vitamins or traditional medications during the STREAM trial without first consulting the trial team

Drug interactions Foods that may interact with the STREAM trial medicines include: Oranges Grapefruit Tuna Aged Cheese Smoked or cured meat Alcohol To avoid interactions, participants should ask their trial doctor or pharmacist about required changes to their diet

Pregnancy Medicines can be transferred to babies via breast milk or may interfere with development of babies during pregnancy We do not know if the medicines in STREAM are safe during pregnancy Female participants must notify the STREAM trial team if they think they may be pregnant. Women who fall pregnant during the trial will be discontinued from trial medication and will complete their treatment as part of the National TB program.

Reminders A patient’s STREAM treatment will depend on which treatment group (A,B,C and D) they are in Participants should store and take trial medicines as directed by the STREAM trial team Remember, medicines only work if they are taken Participants should talk to the STREAM trial team if they have any questions about their treatment or if they have any side effects from taking their pills

Thank you!