Trial Outcomes & Findings for A Phase 1 Study in Patients With Relapsed or Refractory Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma (NCT NCT01950364)

NCT ID: NCT01950364

Last Updated: 2016-05-11

Results Overview

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The lower limit of Quantification (LLQ) for all the observations was 0.01 nanogram/milliliter (ng/mL).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 20 participants
• Primary outcome timeframe: Cycle 1: Predose
• Results posted on: 2016-05-11

Participant Flow

Participants took part in the study at 5 investigative sites in Belgium, Lithuania and Spain from 27 November 2013 to 16 June 2015.

Participants with a historical diagnosis of relapsed or refractory classical hodgkin lymphoma (HL) or relapsed or refractory systemic anaplastic large cell lymphoma (sALCL) were enrolled in 1 of 2 treatment groups: Brentuximab vedotin; Brentuximab vedotin + Rifampicin.

Participant milestones

Measure	Brentuximab Vedotin Brentuximab vedotin 1.8 milligram per kilogram (mg/kg), injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 milligram (mg), capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Overall Study STARTED	10	10
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	10	10

Reasons for withdrawal

Measure	Brentuximab Vedotin Brentuximab vedotin 1.8 milligram per kilogram (mg/kg), injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 milligram (mg), capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Overall Study Adverse Event	3	0
Overall Study Stem Cell Transplant	2	6
Overall Study Disease Progression	5	2
Overall Study Withdrawal by Subject	0	1
Overall Study Protocol Violation	0	1

Baseline Characteristics

A Phase 1 Study in Patients With Relapsed or Refractory Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma

Baseline characteristics by cohort

Measure	Brentuximab Vedotin n=10 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=10 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.	Total n=20 Participants Total of all reporting groups
Age, Continuous	42.3 years STANDARD_DEVIATION 12.15 • n=5 Participants	40.1 years STANDARD_DEVIATION 9.13 • n=7 Participants	41.2 years STANDARD_DEVIATION 10.52 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized White	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment Spain	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Belgium	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Lithuania	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Weight	71.11 kilogram (kg) STANDARD_DEVIATION 17.056 • n=5 Participants	76.84 kilogram (kg) STANDARD_DEVIATION 24.213 • n=7 Participants	73.98 kilogram (kg) STANDARD_DEVIATION 20.595 • n=5 Participants
Height	169.9 centimeter (cm) STANDARD_DEVIATION 3.80 • n=5 Participants	169.7 centimeter (cm) STANDARD_DEVIATION 6.45 • n=7 Participants	169.8 centimeter (cm) STANDARD_DEVIATION 5.15 • n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Disease Type Hodgkin lymphoma	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants
Disease Type sALCL	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Months from Initial Diagnosis to First Dose	34.7 months STANDARD_DEVIATION 31.23 • n=5 Participants	61.9 months STANDARD_DEVIATION 46.96 • n=7 Participants	48.3 months STANDARD_DEVIATION 41.25 • n=5 Participants
Ann Arbor Stage I	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Ann Arbor Stage II	2 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants
Ann Arbor Stage III	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Ann Arbor Stage IV	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 1: Predose

Population: Pharmacokinetic (PK) analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The lower limit of Quantification (LLQ) for all the observations was 0.01 nanogram/milliliter (ng/mL).

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, Predose MMAE	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, Predose C4	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, Predose C5	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, Predose C7	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, Predose C8	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, Predose C13	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 2: Predose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, Predose MMAE	0.0919 ng/mL Standard Deviation 0.05695	0.0795 ng/mL Standard Deviation 0.14220
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, Predose C4	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, Predose C5	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, Predose C7	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, Predose C8	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, Predose C13	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 3: Predose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, Predose MMAE	0.1046 ng/mL Standard Deviation 0.10840	0.0727 ng/mL Standard Deviation 0.05936
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, Predose C4	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, Predose C5	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, Predose C7	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, Predose C8	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, Predose C13	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 1: 0.5 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 0.5 Hour Postdose MMAE	0.3902 ng/mL Standard Deviation 1.33635	0.2149 ng/mL Standard Deviation 0.43900
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 0.5 Hour Postdose C4	0.0184 ng/mL Standard Deviation 0.00613	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 0.5 Hour Postdose C5	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 0.5 Hour Postdose C7	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 0.5 Hour Postdose C8	0.0267 ng/mL Standard Deviation 0.02119	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 0.5 Hour Postdose C13	0.0108 ng/mL Standard Deviation 0.00360	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 2: 0.5 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, 0.5 Hour Postdose MMAE	0.3119 ng/mL Standard Deviation 1.69249	0.2929 ng/mL Standard Deviation 1.39185
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, 0.5 Hour Postdose C4	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, 0.5 Hour Postdose C5	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, 0.5 Hour Postdose C7	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, 0.5 Hour Postdose C8	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	0.0228 ng/mL Standard Deviation 0.00760
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, 0.5 Hour Postdose C13	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 3: 0.5 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 0.5 Hour Postdose MMAE	0.3307 ng/mL Standard Deviation 2.33539	0.2577 ng/mL Standard Deviation 0.26736
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 0.5 Hour Postdose C4	0.0256 ng/mL Standard Deviation 0.00905	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 0.5 Hour Postdose C5	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 0.5 Hour Postdose C7	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 0.5 Hour Postdose C8	0.0323 ng/mL Standard Deviation 0.03266	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 0.5 Hour Postdose C13	0.0210 ng/mL Standard Deviation 0.00742	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 1: 4 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 4 Hour Postdose MMAE	2.2778 ng/mL Standard Deviation 4.42089	1.7836 ng/mL Standard Deviation 0.93129
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 4 Hour Postdose C4	0.0547 ng/mL Standard Deviation 0.02737	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 4 Hour Postdose C5	0.0254 ng/mL Standard Deviation 0.01326	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 4 Hour Postdose C7	0.0195 ng/mL Standard Deviation 0.01293	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 4 Hour Postdose C8	0.0557 ng/mL Standard Deviation 0.05631	0.0160 ng/mL Standard Deviation 0.00921
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 4 Hour Postdose C13	0.0151 ng/mL Standard Deviation 0.00752	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 3: 4 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 4 Hour Postdose MMAE	1.7171 ng/mL Standard Deviation 4.42914	1.4529 ng/mL Standard Deviation 1.36620
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 4 Hour Postdose C4	0.0397 ng/mL Standard Deviation 0.01323	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 4 Hour Postdose C5	0.0163 ng/mL Standard Deviation 0.00804	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 4 Hour Postdose C7	0.0118 ng/mL Standard Deviation 0.00600	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 4 Hour Postdose C8	0.0446 ng/mL Standard Deviation 0.05011	0.0190 ng/mL Standard Deviation 0.01265
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 4 Hour Postdose C13	0.0191 ng/mL Standard Deviation 0.00637	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 1: 24 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 24 Hour Postdose MMAE	3.7950 ng/mL Standard Deviation 4.12446	3.1227 ng/mL Standard Deviation 2.38909
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 24 Hour Postdose C4	0.0443 ng/mL Standard Deviation 0.05328	0.0191 ng/mL Standard Deviation 0.00637
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 24 Hour Postdose C5	0.0218 ng/mL Standard Deviation 0.02814	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 24 Hour Postdose C7	0.0206 ng/mL Standard Deviation 0.01477	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 24 Hour Postdose C8	0.0805 ng/mL Standard Deviation 0.06986	0.0196 ng/mL Standard Deviation 0.01702
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 24 Hour Postdose C13	0.0142 ng/mL Standard Deviation 0.00660	0.0113 ng/mL Standard Deviation 0.00377

PRIMARY outcome

Timeframe: Cycle 3: 24 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 24 Hour Postdose MMAE	3.2336 ng/mL Standard Deviation 2.26369	2.2558 ng/mL Standard Deviation 1.60345
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 24 Hour Postdose C4	0.0200 ng/mL Standard Deviation 0.01071	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 24 Hour Postdose C5	0.0203 ng/mL Standard Deviation 0.01109	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 24 Hour Postdose C7	0.0164 ng/mL Standard Deviation 0.00868	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 24 Hour Postdose C8	0.0715 ng/mL Standard Deviation 0.04523	0.0177 ng/mL Standard Deviation 0.01284
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 24 Hour Postdose C13	0.0105 ng/mL Standard Deviation 0.00371	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 1: 48 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 48 Hour Postdose MMAE	4.2140 ng/mL Standard Deviation 3.69470	3.3727 ng/mL Standard Deviation 2.61792
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 48 Hour Postdose C4	0.0424 ng/mL Standard Deviation 0.05259	0.0128 ng/mL Standard Deviation 0.00565
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 48 Hour Postdose C5	0.0168 ng/mL Standard Deviation 0.02553	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 48 Hour Postdose C7	0.0187 ng/mL Standard Deviation 0.01608	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 48 Hour Postdose C8	0.0959 ng/mL Standard Deviation 0.06780	0.0210 ng/mL Standard Deviation 0.01455
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 48 Hour Postdose C13	0.0134 ng/mL Standard Deviation 0.00763	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 3: 48 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 48 Hour Postdose MMAE	3.4733 ng/mL Standard Deviation 2.17792	2.2156 ng/mL Standard Deviation 1.70890
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 48 Hour Postdose C4	0.0193 ng/mL Standard Deviation 0.01407	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 48 Hour Postdose C5	0.0198 ng/mL Standard Deviation 0.01316	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 48 Hour Postdose C7	0.0170 ng/mL Standard Deviation 0.01112	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 48 Hour Postdose C8	0.0746 ng/mL Standard Deviation 0.06162	0.0195 ng/mL Standard Deviation 0.01114
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 48 Hour Postdose C13	0.0124 ng/mL Standard Deviation 0.00438	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 1: 72 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 72 Hour Postdose MMAE	3.8931 ng/mL Standard Deviation 3.61834	3.0948 ng/mL Standard Deviation 2.03516
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 72 Hour Postdose C4	0.0501 ng/mL Standard Deviation 0.06242	0.0127 ng/mL Standard Deviation 0.00423
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 72 Hour Postdose C5	0.0190 ng/mL Standard Deviation 0.02664	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 72 Hour Postdose C7	0.0241 ng/mL Standard Deviation 0.01640	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 72 Hour Postdose C8	0.0899 ng/mL Standard Deviation 0.06688	0.0187 ng/mL Standard Deviation 0.01111
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 72 Hour Postdose C13	0.0133 ng/mL Standard Deviation 0.00644	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 3: 72 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 72 Hour Postdose MMAE	3.3047 ng/mL Standard Deviation 2.14127	1.9732 ng/mL Standard Deviation 1.32391
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 72 Hour Postdose C4	0.0310 ng/mL Standard Deviation 0.01563	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 72 Hour Postdose C5	0.0256 ng/mL Standard Deviation 0.01510	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 72 Hour Postdose C7	0.0168 ng/mL Standard Deviation 0.01126	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 72 Hour Postdose C8	0.0728 ng/mL Standard Deviation 0.04348	0.0187 ng/mL Standard Deviation 0.01079
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 72 Hour Postdose C13	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 1: 96 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 96 Hour Postdose MMAE	2.9148 ng/mL Standard Deviation 1.70500	3.2956 ng/mL Standard Deviation 2.97022
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 96 Hour Postdose C4	0.0136 ng/mL Standard Deviation 0.00481	0.1420 ng/mL Standard Deviation 0.04733
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 96 Hour Postdose C5	0.0120 ng/mL Standard Deviation 0.00643	0.0593 ng/mL Standard Deviation 0.01977
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 96 Hour Postdose C7	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	0.0374 ng/mL Standard Deviation 0.01247
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 96 Hour Postdose C8	0.0660 ng/mL Standard Deviation 0.04349	0.0228 ng/mL Standard Deviation 0.06198
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 96 Hour Postdose C13	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	0.0108 ng/mL Standard Deviation 0.00360

PRIMARY outcome

Timeframe: Cycle 3: 96 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 96 Hour Postdose MMAE	2.4449 ng/mL Standard Deviation 1.44334	2.2344 ng/mL Standard Deviation 1.81211
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 96 Hour Postdose C4	0.0140 ng/mL Standard Deviation 0.00704	0.0418 ng/mL Standard Deviation 0.01393
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 96 Hour Postdose C5	0.0205 ng/mL Standard Deviation 0.01017	0.0294 ng/mL Standard Deviation 0.00980
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 96 Hour Postdose C7	0.0121 ng/mL Standard Deviation 0.00428	0.0252 ng/mL Standard Deviation 0.00840
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 96 Hour Postdose C8	0.0622 ng/mL Standard Deviation 0.04328	0.0392 ng/mL Standard Deviation 0.04163
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 96 Hour Postdose C13	0.0105 ng/mL Standard Deviation 0.00371	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 1: 144 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 144 Hour Postdose MMAE	2.3326 ng/mL Standard Deviation 1.45619	1.7990 ng/mL Standard Deviation 0.89695
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 144 Hour Postdose C4	0.0297 ng/mL Standard Deviation 0.02569	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 144 Hour Postdose C5	0.0174 ng/mL Standard Deviation 0.01006	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 144 Hour Postdose C7	0.0196 ng/mL Standard Deviation 0.00693	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 144 Hour Postdose C8	0.0497 ng/mL Standard Deviation 0.02722	0.0120 ng/mL Standard Deviation 0.00542
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 144 Hour Postdose C13	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 3: 144 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 144 Hour Postdose MMAE	2.0555 ng/mL Standard Deviation 1.07315	1.2920 ng/mL Standard Deviation 0.75690
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 144 Hour Postdose C4	0.0198 ng/mL Standard Deviation 0.00976	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 144 Hour Postdose C5	0.0140 ng/mL Standard Deviation 0.00760	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 144 Hour Postdose C7	0.0137 ng/mL Standard Deviation 0.00484	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 144 Hour Postdose C8	0.0441 ng/mL Standard Deviation 0.02147	0.0145 ng/mL Standard Deviation 0.00648
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 144 Hour Postdose C13	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 1: 336 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 336 Hour Postdose MMAE	0.3130 ng/mL Standard Deviation 0.15743	0.2723 ng/mL Standard Deviation 0.16544
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 336 Hour Postdose C4	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 336 Hour Postdose C5	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 336 Hour Postdose C7	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 336 Hour Postdose C8	0.0127 ng/mL Standard Deviation 0.00672	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 336 Hour Postdose C13	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 3: 336 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 336 Hour Postdose MMAE	0.4258 ng/mL Standard Deviation 0.30565	0.2578 ng/mL Standard Deviation 0.10847
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 336 Hour Postdose C4	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 336 Hour Postdose C5	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 336 Hour Postdose C7	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 336 Hour Postdose C8	0.0168 ng/mL Standard Deviation 0.01011	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 336 Hour Postdose C13	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 3: 480 hour postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 480 Hour Postdose MMAE	0.1189 ng/mL Standard Deviation 0.15808	0.0941 ng/mL Standard Deviation 0.03974
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 480 Hour Postdose C4	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 480 Hour Postdose C5	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 480 Hour Postdose C7	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 480 Hour Postdose C8	0.0114 ng/mL Standard Deviation 0.00431	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 480 Hour Postdose C13	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 1: Predose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, Predose MMAE	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	7.8900 ng Standard Deviation 2.63000
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, Predose C4	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, Predose C5	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, Predose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, Predose C8	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	0.0712 ng Standard Deviation 0.02373
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, Predose C13	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 1: 0-24 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 0-24 Hours Postdose MMAE	12.5668 ng Standard Deviation 5.31374	12.5020 ng Standard Deviation 6.85958
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 0-24 Hours Postdose C4	0.0878 ng Standard Deviation 0.13223	0.0521 ng Standard Deviation 0.02335
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 0-24 Hours Postdose C5	0.0883 ng Standard Deviation 0.10135	0.0254 ng Standard Deviation 0.00847
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 0-24 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 0-24 Hours Postdose C8	0.5967 ng Standard Deviation 0.56221	0.1047 ng Standard Deviation 0.07785
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 0-24 Hours Postdose C13	0.0786 ng Standard Deviation 0.11460	0.0456 ng Standard Deviation 0.03714

PRIMARY outcome

Timeframe: Cycle 1: 24-48 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 24-48 Hours Postdose MMAE	12.6225 ng Standard Deviation 6.93735	11.7995 ng Standard Deviation 6.20286
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 24-48 Hours Postdose C4	0.0690 ng Standard Deviation 0.10935	0.0392 ng Standard Deviation 0.03010
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 24-48 Hours Postdose C5	0.0863 ng Standard Deviation 0.09138	0.0277 ng Standard Deviation 0.01700
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 24-48 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 24-48 Hours Postdose C8	0.7275 ng Standard Deviation 0.59716	0.1568 ng Standard Deviation 0.08381
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 24-48 Hours Postdose C13	0.0722 ng Standard Deviation 0.07482	0.0405 ng Standard Deviation 0.03473

PRIMARY outcome

Timeframe: Cycle 1: 48-72 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 48-72 Hours Postdose MMAE	12.4089 ng Standard Deviation 4.49922	11.6600 ng Standard Deviation 5.45329
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 48-72 Hours Postdose C4	0.0812 ng Standard Deviation 0.15006	0.0419 ng Standard Deviation 0.02694
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 48-72 Hours Postdose C5	0.0867 ng Standard Deviation 0.10841	0.0322 ng Standard Deviation 0.01859
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 48-72 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 48-72 Hours Postdose C8	0.7973 ng Standard Deviation 0.38226	0.1189 ng Standard Deviation 0.08494
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 48-72 Hours Postdose C13	0.0786 ng Standard Deviation 0.05672	0.0382 ng Standard Deviation 0.02718

PRIMARY outcome

Timeframe: Cycle 1: 72-96 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 72-96 Hours Postdose MMAE	10.7766 ng Standard Deviation 8.14858	12.8426 ng Standard Deviation 5.93538
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 72-96 Hours Postdose C4	0.0867 ng Standard Deviation 0.16449	0.0427 ng Standard Deviation 0.02848
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 72-96 Hours Postdose C5	0.0882 ng Standard Deviation 0.11202	0.0394 ng Standard Deviation 0.02131
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 72-96 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 72-96 Hours Postdose C8	0.7480 ng Standard Deviation 0.61219	0.1247 ng Standard Deviation 0.08379
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 72-96 Hours Postdose C13	0.0754 ng Standard Deviation 0.06820	0.0415 ng Standard Deviation 0.02723

PRIMARY outcome

Timeframe: Cycle 1: 96-120 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 96-120 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 96-120 Hours Postdose C8	0.7360 ng Standard Deviation 1.02417	0.1034 ng Standard Deviation 0.10563
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 96-120 Hours Postdose MMAE	10.8018 ng Standard Deviation 12.03431	9.5626 ng Standard Deviation 7.26020
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 96-120 Hours Postdose C4	0.0885 ng Standard Deviation 0.11811	0.0414 ng Standard Deviation 0.03529
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 96-120 Hours Postdose C5	0.1053 ng Standard Deviation 0.10639	0.0406 ng Standard Deviation 0.02753
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 96-120 Hours Postdose C13	0.0630 ng Standard Deviation 0.08155	0.0380 ng Standard Deviation 0.03436

PRIMARY outcome

Timeframe: Cycle 1: 120-144 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 120-144 Hours Postdose MMAE	6.7161 ng Standard Deviation 6.13997	7.9830 ng Standard Deviation 4.33309
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 120-144 Hours Postdose C4	0.0730 ng Standard Deviation 0.08387	0.0335 ng Standard Deviation 0.02037
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 120-144 Hours Postdose C5	0.0836 ng Standard Deviation 0.07377	0.0301 ng Standard Deviation 0.01767
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 120-144 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 120-144 Hours Postdose C8	0.4477 ng Standard Deviation 0.56047	0.0910 ng Standard Deviation 0.06044
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 120-144 Hours Postdose C13	0.0551 ng Standard Deviation 0.05107	0.0345 ng Standard Deviation 0.01738

PRIMARY outcome

Timeframe: Cycle 1: 144-168 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 144-168 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 144-168 Hours Postdose C8	0.3916 ng Standard Deviation 0.34491	0.0706 ng Standard Deviation 0.03027
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 144-168 Hours Postdose C13	0.0438 ng Standard Deviation 0.03146	0.0363 ng Standard Deviation 0.01283
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 144-168 Hours Postdose MMAE	5.5693 ng Standard Deviation 3.50945	5.8025 ng Standard Deviation 3.45889
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 144-168 Hours Postdose C4	0.0579 ng Standard Deviation 0.06807	0.0448 ng Standard Deviation 0.02158
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 144-168 Hours Postdose C5	0.0747 ng Standard Deviation 0.05078	0.0287 ng Standard Deviation 0.01527

PRIMARY outcome

Timeframe: Cycle 1: 336-360 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 336-360 Hours Postdose MMAE	1.0727 ng Standard Deviation 0.55233	1.3326 ng Standard Deviation 0.80959
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 336-360 Hours Postdose C4	0.0459 ng Standard Deviation 0.01530	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 336-360 Hours Postdose C5	0.0289 ng Standard Deviation 0.00963	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 336-360 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 336-360 Hours Postdose C8	0.0751 ng Standard Deviation 0.04505	0.0401 ng Standard Deviation 0.02242
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 336-360 Hours Postdose C13	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 1: 480-504 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 480-504 Hours Postdose MMAE	0.4420 ng Standard Deviation 0.30745	0.3505 ng Standard Deviation 0.14592
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 480-504 Hours Postdose C4	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 480-504 Hours Postdose C5	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 480-504 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 480-504 Hours Postdose C8	0.0578 ng Standard Deviation 0.03314	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 480-504 Hours Postdose C13	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 3: Predose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, Predose MMAE	0.3171 ng Standard Deviation 0.33548	0.4227 ng Standard Deviation 0.17918
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, Predose C4	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, Predose C5	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, Predose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, Predose C8	0.0392 ng Standard Deviation 0.02985	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, Predose C13	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 3: 0-24 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 0-24 Hours Postdose MMAE	10.7174 ng Standard Deviation 15.35912	12.4438 ng Standard Deviation 8.86144
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 0-24 Hours Postdose C4	0.0454 ng Standard Deviation 0.07644	0.0451 ng Standard Deviation 0.02977
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 0-24 Hours Postdose C5	0.0509 ng Standard Deviation 0.04623	0.0301 ng Standard Deviation 0.01847
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 0-24 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 0-24 Hours Postdose C8	0.4657 ng Standard Deviation 0.41352	0.1285 ng Standard Deviation 0.17930
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 0-24 Hours Postdose C13	0.0516 ng Standard Deviation 0.07045	0.0676 ng Standard Deviation 0.05022

PRIMARY outcome

Timeframe: Cycle 3: 24-48 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 24-48 Hours Postdose MMAE	11.1360 ng Standard Deviation 6.73693	13.2483 ng Standard Deviation 4.79482
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 24-48 Hours Postdose C4	0.0604 ng Standard Deviation 0.05049	0.0413 ng Standard Deviation 0.03095
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 24-48 Hours Postdose C5	0.0808 ng Standard Deviation 0.06838	0.0311 ng Standard Deviation 0.02021
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 24-48 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 24-48 Hours Postdose C8	0.5750 ng Standard Deviation 0.58196	0.1600 ng Standard Deviation 0.11946
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 24-48 Hours Postdose C13	0.0637 ng Standard Deviation 0.05102	0.0507 ng Standard Deviation 0.03607

PRIMARY outcome

Timeframe: Cycle 3: 48-72 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 48-72 Hours Postdose MMAE	12.7267 ng Standard Deviation 8.96991	13.8072 ng Standard Deviation 8.63973
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 48-72 Hours Postdose C4	0.0620 ng Standard Deviation 0.06222	0.0524 ng Standard Deviation 0.04691
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 48-72 Hours Postdose C5	0.0746 ng Standard Deviation 0.09237	0.0406 ng Standard Deviation 0.03034
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 48-72 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 48-72 Hours Postdose C8	0.6950 ng Standard Deviation 0.83588	0.1598 ng Standard Deviation 0.14846
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 48-72 Hours Postdose C13	0.0632 ng Standard Deviation 0.06480	0.0746 ng Standard Deviation 0.05134

PRIMARY outcome

Timeframe: Cycle 3: 72-96 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 72-96 Hours Postdose MMAE	11.2527 ng Standard Deviation 8.65574	12.2263 ng Standard Deviation 6.09003
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 72-96 Hours Postdose C4	0.0702 ng Standard Deviation 0.07079	0.0611 ng Standard Deviation 0.05055
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 72-96 Hours Postdose C5	0.0937 ng Standard Deviation 0.10757	0.0437 ng Standard Deviation 0.03084
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 72-96 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 72-96 Hours Postdose C8	0.5276 ng Standard Deviation 0.95507	0.1510 ng Standard Deviation 0.11532
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 72-96 Hours Postdose C13	0.0573 ng Standard Deviation 0.07734	0.0564 ng Standard Deviation 0.03759

PRIMARY outcome

Timeframe: Cycle 3: 96-120 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 96-120 Hours Postdose MMAE	8.3817 ng Standard Deviation 7.78279	8.1426 ng Standard Deviation 7.29530
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 96-120 Hours Postdose C4	0.0710 ng Standard Deviation 0.05912	0.0512 ng Standard Deviation 0.04137
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 96-120 Hours Postdose C5	0.0916 ng Standard Deviation 0.08893	0.0435 ng Standard Deviation 0.02885
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 96-120 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 96-120 Hours Postdose C8	0.5198 ng Standard Deviation 0.79634	0.1088 ng Standard Deviation 0.09569
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 96-120 Hours Postdose C13	0.0607 ng Standard Deviation 0.06838	0.0524 ng Standard Deviation 0.03619

PRIMARY outcome

Timeframe: Cycle 3: 120-144 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 120-144 Hours Postdose MMAE	7.3500 ng Standard Deviation 3.78427	7.5871 ng Standard Deviation 4.66863
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 120-144 Hours Postdose C4	0.0461 ng Standard Deviation 0.03666	0.0520 ng Standard Deviation 0.03870
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 120-144 Hours Postdose C5	0.0657 ng Standard Deviation 0.04811	0.0342 ng Standard Deviation 0.02508
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 120-144 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 120-144 Hours Postdose C8	0.4700 ng Standard Deviation 0.37131	0.0869 ng Standard Deviation 0.07672
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 120-144 Hours Postdose C13	0.0386 ng Standard Deviation 0.03212	0.0429 ng Standard Deviation 0.02820

PRIMARY outcome

Timeframe: Cycle 3: 144-168 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 144-168 Hours Postdose MMAE	6.1125 ng Standard Deviation 3.83207	4.6823 ng Standard Deviation 2.80767
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 144-168 Hours Postdose C4	0.0538 ng Standard Deviation 0.04252	0.0562 ng Standard Deviation 0.02674
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 144-168 Hours Postdose C5	0.0662 ng Standard Deviation 0.06110	0.0308 ng Standard Deviation 0.01718
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 144-168 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 144-168 Hours Postdose C8	0.3485 ng Standard Deviation 0.45898	0.0651 ng Standard Deviation 0.03984
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 144-168 Hours Postdose C13	0.0402 ng Standard Deviation 0.04117	0.0481 ng Standard Deviation 0.01603

PRIMARY outcome

Timeframe: Cycle 3: 336-360 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 336-360 Hours Postdose MMAE	1.2811 ng Standard Deviation 1.55068	0.8271 ng Standard Deviation 0.43597
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 336-360 Hours Postdose C4	0.0377 ng Standard Deviation 0.01812	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 336-360 Hours Postdose C5	0.0347 ng Standard Deviation 0.02457	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 336-360 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 336-360 Hours Postdose C8	0.0734 ng Standard Deviation 0.10958	0.0277 ng Standard Deviation 0.01306
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 336-360 Hours Postdose C13	0.0227 ng Standard Deviation 0.00757	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

PRIMARY outcome

Timeframe: Cycle 3: 480-504 hours postdose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 480-504 Hours Postdose MMAE	0.4660 ng Standard Deviation 0.41713	0.3334 ng Standard Deviation 0.25074
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 480-504 Hours Postdose C4	0.0248 ng Standard Deviation 0.00827	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 480-504 Hours Postdose C5	0.0377 ng Standard Deviation 0.01257	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 480-504 Hours Postdose C7	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 480-504 Hours Postdose C8	0.0620 ng Standard Deviation 0.04967	0.0221 ng Standard Deviation 0.00737
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 480-504 Hours Postdose C13	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.

SECONDARY outcome

Timeframe: Cycle 1 and 3: Predose, 0.5, 4, 72, 336 hours post-dose; Cycle 2: Predose, 0.5 hours post-dose; Cycle 3: 480 hours post-dose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

The LLQ for all the observations was 12.5 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Serum Concentrations of Antibody-drug Conjugate (ADC) Cycle 1, Predose	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Serum Concentrations of Antibody-drug Conjugate (ADC) Cycle 1, 0.5 hour	29609.7759 ng/mL Standard Deviation 11865.35702	33125.0025 ng/mL Standard Deviation 10398.79403
Serum Concentrations of Antibody-drug Conjugate (ADC) Cycle 1, 4 hour	24398.6482 ng/mL Standard Deviation 8092.41448	24533.2372 ng/mL Standard Deviation 6767.70744
Serum Concentrations of Antibody-drug Conjugate (ADC) Cycle 1, 72 hour	4265.7542 ng/mL Standard Deviation 2880.39660	5958.0569 ng/mL Standard Deviation 1788.56378
Serum Concentrations of Antibody-drug Conjugate (ADC) Cycle 1, 336 hour	1167.0713 ng/mL Standard Deviation 740.05650	1108.6515 ng/mL Standard Deviation 376.81123
Serum Concentrations of Antibody-drug Conjugate (ADC) Cycle 2, Predose	794.3851 ng/mL Standard Deviation 10732.46886	435.1550 ng/mL Standard Deviation 303.25245
Serum Concentrations of Antibody-drug Conjugate (ADC) Cycle 2, 0.5 hour	16032.6494 ng/mL Standard Deviation 15714.59821	31627.2566 ng/mL Standard Deviation 6716.71906
Serum Concentrations of Antibody-drug Conjugate (ADC) Cycle 3, Predose	611.0573 ng/mL Standard Deviation 786.52082	536.3692 ng/mL Standard Deviation 524.72923
Serum Concentrations of Antibody-drug Conjugate (ADC) Cycle 3, 0.5 hour	20991.9618 ng/mL Standard Deviation 12662.05087	33040.2245 ng/mL Standard Deviation 6295.45517
Serum Concentrations of Antibody-drug Conjugate (ADC) Cycle 3, 4 hour	15378.8274 ng/mL Standard Deviation 9550.99903	24496.7203 ng/mL Standard Deviation 4212.84997
Serum Concentrations of Antibody-drug Conjugate (ADC) Cycle 3, 72 hour	3258.7237 ng/mL Standard Deviation 3358.78504	4262.0364 ng/mL Standard Deviation 2431.24647
Serum Concentrations of Antibody-drug Conjugate (ADC) Cycle 3, 336 hour	1381.2290 ng/mL Standard Deviation 1224.66857	1363.9488 ng/mL Standard Deviation 789.04877
Serum Concentrations of Antibody-drug Conjugate (ADC) Cycle 3, 480 hour	648.2492 ng/mL Standard Deviation 1065.26404	734.5557 ng/mL Standard Deviation 634.23889

SECONDARY outcome

Timeframe: Cycle 1 and 3: Predose, 0.5, 4, 72, 336 hours post-dose; Cycle 2: Predose, 0.5 hours post-dose; Cycle 3: 480 hours post-dose

Population: PK analysis set included all participants who received brentuximab vedotin at 1.8 mg/kg throughout Cycles 1 to 3 and had sufficient dosing and PK data to reliably estimate PK parameters.

The LLQ for all the observations was 12.5 ng/mL.

Outcome measures

Measure	Brentuximab Vedotin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=9 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Serum Concentration of Total Antibody (TAb) Cycle 1, Predose	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.	NA ng/mL Standard Deviation NA None of the participants had data above LLQ and as per the predefined protocol results were to be summarized only for observations above LLQ, hence, data was not reported.
Serum Concentration of Total Antibody (TAb) Cycle 1, 0.5 hour	30874.4957 ng/mL Standard Deviation 11904.18494	30884.9074 ng/mL Standard Deviation 9956.67036
Serum Concentration of Total Antibody (TAb) Cycle 1, 4 hour	28577.3869 ng/mL Standard Deviation 9365.88746	28865.4674 ng/mL Standard Deviation 8192.50406
Serum Concentration of Total Antibody (TAb) Cycle 1, 72 hour	9931.2943 ng/mL Standard Deviation 4973.74692	11626.2147 ng/mL Standard Deviation 4396.55604
Serum Concentration of Total Antibody (TAb) Cycle 1, 336 hour	2898.2924 ng/mL Standard Deviation 1831.73997	3066.5859 ng/mL Standard Deviation 1017.84204
Serum Concentration of Total Antibody (TAb) Cycle 2, Predose	2055.3871 ng/mL Standard Deviation 10312.91280	1363.8319 ng/mL Standard Deviation 904.27346
Serum Concentration of Total Antibody (TAb) Cycle 2, 0.5 hour	17378.2105 ng/mL Standard Deviation 17543.51968	31583.7793 ng/mL Standard Deviation 7742.69918
Serum Concentration of Total Antibody (TAb) Cycle 3, Predose	1361.3147 ng/mL Standard Deviation 1592.89993	1517.6506 ng/mL Standard Deviation 1200.68646
Serum Concentration of Total Antibody (TAb) Cycle 3, 0.5 hour	15974.3723 ng/mL Standard Deviation 12467.10368	33892.4731 ng/mL Standard Deviation 10595.70675
Serum Concentration of Total Antibody (TAb) Cycle 3, 4 hour	11609.1430 ng/mL Standard Deviation 14719.69968	27548.1773 ng/mL Standard Deviation 7219.71925
Serum Concentration of Total Antibody (TAb) Cycle 3, 72 hour	13594.2016 ng/mL Standard Deviation 7492.70742	9588.9374 ng/mL Standard Deviation 5665.38218
Serum Concentration of Total Antibody (TAb) Cycle 3, 336 hour	3206.6925 ng/mL Standard Deviation 3000.22116	3628.9175 ng/mL Standard Deviation 1802.66091
Serum Concentration of Total Antibody (TAb) Cycle 3, 480 hour	1329.0886 ng/mL Standard Deviation 2024.17213	1866.5746 ng/mL Standard Deviation 1326.12113

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (30 days after Cycle 16)

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. AEs included both SAE and non-SAE.

Outcome measures

Measure	Brentuximab Vedotin n=10 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=10 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) AEs	9 participants	9 participants
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	4 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 and 3

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

Participants with positive ATA at both Cycle 1 and 3, negative ATA at both Cycle 1 and 3, and transient positive (positive at one time point, but negative at the other) ATA for brentuximab vedotin were reported.

Outcome measures

Measure	Brentuximab Vedotin n=10 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=10 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Number of Participants With Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin Negative in both Cycle 1 and 3	5 participants	7 participants
Number of Participants With Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin Positive in both Cycle 1 and 3	1 participants	0 participants
Number of Participants With Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin Transient Positive	2 participants	2 participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (30 Days after Cycle 16)

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

The number of participants with any markedly abnormal standard safety laboratory values collected throughout study.

Outcome measures

Measure	Brentuximab Vedotin n=10 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=10 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Number of Participants With Markedly Abnormal Laboratory Values	5 participants	5 participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (30 Days after Cycle 16)

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

Vital signs included body temperature, body weight, blood pressure and heart rate.

Outcome measures

Measure	Brentuximab Vedotin n=10 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=10 Participants Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	1 participants	2 participants

Adverse Events

Brentuximab Vedotin

Serious events: 4 serious events

Other events: 9 other events

Deaths: 0 deaths

Brentuximab Vedotin + Rifampicin

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Brentuximab Vedotin n=10 participants at risk Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=10 participants at risk Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
General disorders Thrombosis in device	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
General disorders Pyrexia	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Infections and infestations Staphylococcal infection	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Infections and infestations Pulmonary tuberculosis	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Respiratory, thoracic and mediastinal disorders Respiratory failure	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Infections and infestations Pneumocystis jirovecii pneumonia	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Nervous system disorders Neuralgia	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.

Other adverse events

Measure	Brentuximab Vedotin n=10 participants at risk Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses.	Brentuximab Vedotin + Rifampicin n=10 participants at risk Brentuximab vedotin 1.8 mg/kg, injection, intravenously, every 3 weeks on Day 1 of each 21-day treatment cycle up to a maximum of 16 brentuximab vedotin doses and rifampicin, 600 mg, capsules, orally, once daily from Day 1 of treatment Cycle 0 through Day 21 of treatment cycle 3.
Skin and subcutaneous tissue disorders Pruritus	30.0% 3/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	30.0% 3/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Blood and lymphatic system disorders Neutropenia	30.0% 3/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Blood and lymphatic system disorders Anaemia	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Gastrointestinal disorders Diarrhoea	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Blood and lymphatic system disorders Eosinophilia	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Metabolism and nutrition disorders Hypokalaemia	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Metabolism and nutrition disorders Hypomagnesaemia	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Nervous system disorders Peripheral sensory neuropathy	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
General disorders Pyrexia	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Cardiac disorders Sinus tachycardia	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
General disorders Fatigue	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Infections and infestations Herpes zoster	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Metabolism and nutrition disorders Hyponatraemia	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Gastrointestinal disorders Nausea	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Nervous system disorders Peripheral motor neuropathy	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Blood and lymphatic system disorders Thrombocytopenia	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Skin and subcutaneous tissue disorders Toxic skin eruption	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Gastrointestinal disorders Vomiting	20.0% 2/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Gastrointestinal disorders Abdominal distension	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Gastrointestinal disorders Abdominal pain upper	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Gastrointestinal disorders Anal haemorrhage	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Psychiatric disorders Anxiety	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
General disorders Asthenia	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Musculoskeletal and connective tissue disorders Back pain	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Investigations Blood urea increased	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Investigations Body temperature increased	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Musculoskeletal and connective tissue disorders Bone pain	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
General disorders Chills	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Infections and infestations Cystitis	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Metabolism and nutrition disorders Decreased appetite	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Psychiatric disorders Depression	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Metabolism and nutrition disorders Diabetes mellitus	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Nervous system disorders Dizziness	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Eye disorders Dry eye	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Skin and subcutaneous tissue disorders Erythema	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Eye disorders Glaucoma	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Metabolism and nutrition disorders Hyperglycaemia	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Metabolism and nutrition disorders Hypocalcaemia	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Metabolism and nutrition disorders Hypochloraemia	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
General disorders Injection site pain	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Psychiatric disorders Insomnia	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Musculoskeletal and connective tissue disorders Joint stiffness	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Blood and lymphatic system disorders Leukopenia	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
General disorders Local swelling	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
General disorders Localised oedema	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Infections and infestations Lung infection	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Musculoskeletal and connective tissue disorders Muscle spasms	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
General disorders Oedema peripheral	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Infections and infestations Oral herpes	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Respiratory, thoracic and mediastinal disorders Productive cough	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Injury, poisoning and procedural complications Scratch	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Respiratory, thoracic and mediastinal disorders Sneezing	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Infections and infestations Viral infection	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Investigations Weight increased	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.
Injury, poisoning and procedural complications Wound	0.00% 0/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.	10.0% 1/10 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (30 days after Cycle 16). Serious and non-serious AEs were collected from first dose through 30 days after the last dose (Cycle 16). Beginning on Cycle 4 Day 1, only AEs with Grade 3 were recorded. Exceptions: New onset AEs of Grade 1-2 were recorded if they met criteria for SAEs or resulted in dose modification; PN events will be recorded regardless of severity grade.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
• Publication restrictions are in place

Restriction type: OTHER