Envarsus XR Compared to Immediate Release Tacrolimus

The CIRS is a questionnaire that assesses five symptoms (from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events \[PRO-CTCAE\]) that have been shown to be associated with calcineurin inhibitors. These symptoms include trembling hands, muscle cramps, muscle weakness, swollen gums, and increased hair growth. Each symptom is based on symptom severity in the last 7 days scaled from 0 (none) - 4 (very severe). The cumulative score ranges from 0-20, with higher scores indicating a worse outcome.

Time frame: Baseline; 12 months

Population: 20 subjects in the Tacrolimus arm and 45 subjects in the Envarsus arm did not complete the CIRS questionnaire at the 12-month mark, therefore no data exists for those 65 subjects.

Number of adverse events reported

Time frame: 12 months

The PROMIS-29 questionnaire measures physical and mental health outcomes for patients. Patients responded to 29 questions in seven categories: physical function, pain interference, depressive symptoms, anxiety, ability to participate in social activities, and sleep disturbance. Scores were scaled so that an average healthy person would score 50 points. A higher score represents a worse outcome. Patient questionnaire responses are scored using the PROMIS-29 scoring algorithm. Scores were scaled to a mean of 50 for a healthy reference population with a standard deviation of 10.

Time frame: Baseline; 12 months

Population: 36 subjects in the Tacrolimus arm and 56 subjects in the Envarsus arm did not complete the PROMIS-29 questionnaire at the 12-month mark, therefore no data exists for those 92 subjects.

Defined as the percentage of prescribed doses taken each day

Time frame: 12 months

Population: Data for this outcome measure were not collected in either treatment arm. The electronic data capture system was configured incorrectly and did not include the fields required to record medication adherence. As a result, the study team was unable to collect adherence data for any participants.

Measured by item GP5 (I am bothered by side effects of treatment) from the FACT-G Questionnaire. FACT-G GP5 is a single-item measure from the Functional Assessment of Cancer Therapy (FACT) scale, specifically designed to assess patient-reported tolerability to cancer treatments. Subjects are asked to rate their level of tolerability on a scale of 0 (not at all bothered) to 4 (very much bothered), with a higher score indicating a worse outcome.

Time frame: Baseline; 12 months

Population: 21 subjects in the Tacrolimus arm and 45 subjects in the Envarsus arm did not complete the FACT-G questionnaire at the 12-month mark, therefore no data exists for those 66 subjects.

Question 14 of the Treatment Satisfaction Questionnaire for Medication measures medication satisfaction on a 7-item scale ranging from 0 (Extremely Dissatisfied) to 7 (Extremely Satisfied), with higher scores indicating better satisfaction.

Time frame: Baseline; 12 months

Population: 99 subjects in the Tacrolimus arm and 116 subjects in the Envarsus arm did not complete the Treatment Satisfaction questionnaire at the 12-month mark, therefore no data exists for those 215 subjects.

The change in the number of subjects with a reduction in a CIRS item score from a severe or very severe score (3 to 4) to a mild to moderate (1 or 2) score from 4 months to 12 months.

Time frame: 4 months; 12 months

Population: 29 subjects in the Tacrolimus arm and 54 subjects in the Envarsus arm did not complete the CIRS questionnaire at the 4-month mark, therefore no data exists for those 83 subjects. 2 subjects in the Tacrolimus arm only filled out a portion of the survey at the 4-month mark, due to this those two subjects were not included in the analysis for this outcome as a change in reduction of symptoms from very severe/severe to mild/moderate could not be calculated.

The change in the number of subjects with a reduction in any single CIRS item by 1 point or greater from 4 months to 12 months.

Time frame: 4 months; 12 months.

Population: 29 subjects in the Tacrolimus arm and 54 subjects in the Envarsus arm did not complete the CIRS questionnaire at the 4-month mark, therefore no data exists for those 83 subjects.

The change in the severity score in each of the five individual CIRS items: trembling hands, muscle cramps, muscle weakness, swollen gums, and increased hair growth. The CIRS is a questionnaire that assesses five symptoms (from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events \[PRO-CTCAE\]) that have been shown to be associated with calcineurin inhibitors. These symptoms include trembling hands, muscle cramps, muscle weakness, swollen gums, and increased hair growth. Each symptom is based on symptom severity in the last 7 days scaled from 0 (none) - 4 (very severe), with higher scores indicating a worse outcome.

Time frame: Baseline; 12 months

Population: 20 subjects in the Tac arm and 45 subjects in the Envarsus arm didn't complete the CIRS questionnaire at the 12-month mark, therefore no data exists for those 65 subjects. 1 subject in the Tac arm and 1 in the Envarsus arm didn't complete the muscle weakness section of the questionnaire. 1 subject in the Tac arm didn't complete the swollen gums section of the questionnaire. 2 subjects in the Tac arm and 1 in the Envarsus arm didn't complete the hair growth section of the questionnaire.

The change in the transplant related symptoms score in each of the fifteen individual TRS items: change in taste, constipation, diarrhea, swelling in arms or legs, palpitations, dry skin, darkening of skin, blurry vision, headache, insomnia, anxiety, sadness, depression, increase in appetite, and fatigue. The TRS is a multi-item questionnaire capturing 15 symptoms (from PRO-CTCAE) that have been shown to be associated with transplant and general health-related quality of life improvement. These symptoms include change in taste, constipation, diarrhea, swelling in arms or legs, palpitations, dry skin, darkening of skin, blurry vision, headache, insomnia, anxiety, sadness, depression, increase in appetite, and fatigue. Each symptom is based on symptom severity in the last 7 days and scaled from 0 (none) - 4 (very severe), with higher scores indicating a worse outcome.

Time frame: Baseline; 12 months

Population: 20 in Tac arm,45 in XR arm didn't complete TRS at 12months,therefore no data exists for the 65 subjects.1 in XR arm didn't complete taste/palpitation/headache/insomnia/fatigue sections.1 in Tac arm didn't complete appetite/swelling/palpitation/fatigue/anxiety/depression section.3 in XR arm didn't complete diarrhea/depression/sadness sections.2 in Tac arm didn't complete vision/sadness sections.3 in Tac arm didn't complete headache section.8 in Tac arm,7 in XR arm didn't complete darkskin section

Proportion of patients at different adherence thresholds of taking and timing adherences between 4 months and 12 months post transplant will be correlated with the presence or absence of dnDSA by 12 months post-transplant

Time frame: 4 months; 12 months

Population: Data for this outcome measure were not collected in either treatment arm. The electronic data capture system was configured incorrectly and did not include the fields required to record correlation between de novo DSA and degree of taking and timing adherence. As a result, the study team was unable to collect correlation between de novo DSA and degree of taking and timing adherence data on any participant.

Number of subjects in each treatment group with a moderately severe, severe or very severe score (2, 3 or 4) on any CIRS item. The CIRS is a questionnaire that assesses five symptoms (from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events \[PRO-CTCAE\]) that have been shown to be associated with calcineurin inhibitors. These symptoms include trembling hands, muscle cramps, muscle weakness, swollen gums, and increased hair growth. Each symptom is based on symptom severity in the last 7 days scaled from 0 (none) - 4 (very severe). The cumulative score ranges from 0-20, with higher scores indicating a worse outcome.

Time frame: 12 months

Population: 20 subjects in the Tacrolimus arm and 45 subjects in the Envarsus arm did not complete the CIRS questionnaire at the 12-month mark, therefore no data exists for those 65 subjects.

The TRS is a 30-item questionnaire capturing 15 symptoms (from PRO-CTCAE) that have been shown to be associated with transplant and general health-related quality of life improvement. These symptoms include change in taste, constipation, diarrhea, swelling in arms or legs, palpitations, dry skin, darkening of skin, blurry vision, headache, insomnia, anxiety, sadness, discouraged, increase in appetite, and fatigue. Each symptom is based on symptom severity in the last 7 days and scaled from 0 (none) - 4 (very severe). Total scores range from 0 to 120, with higher scores indicating a worse outcome.

Time frame: Baseline; 12 months

Population: 20 subjects in the Tacrolimus arm and 45 subjects in the Envarsus arm did not complete the TRS questionnaire at the 12-month mark, therefore no data exists for those 65 subjects.