Trial Outcomes & Findings for Study of Safety and Efficacy of a Sequential Regimen Consisting of Three Cycles of Fludarabine Followed by Tositumomab and Iodine I 131 Tositumomab (NCT NCT00933335)

NCT ID: NCT00933335

Last Updated: 2017-01-18

Results Overview

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and does not necessarily have to have a causal relationship (association) with this treatment. Therefore, an AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not it was considered to be related to the medicinal product. Laboratory abnormalities were recorded as AEs only if they were associated with clinical sequelae and/or required an intervention.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 38 participants
• Primary outcome timeframe: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST dosimetric dose (DD) (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)
• Results posted on: 2017-01-18

Participant Flow

Participants received fludarabine in the first study phase. Upon completion of this phase, if they met the appropriate criteria, they began the first of 2 phases of radioimmunotherapy: Phase 1, dosimetric dose (DD), administered 6 weeks after Day 1 of the third fludarabine cycle; Phase 2, therapeutic dose, administered 7-14 days after the DD.

Participant milestones

Measure	Received Less Than 3 Cycles of Fludarabine Participants received less than 3 cycles of intravenous (IV) fludarabine monophosphate (25 milligrams/meter\^2/day \[mg/m\^2/day\]) for 5 days every 5 to 6 weeks.	Fludarabine (3 Cycles); TST and Iodine I 131 TST Participants (par.) received 3 cycles of IV fludarabine (FL) monophosphate (25 mg/m\^2/day) for 5 days every 5-6 weeks. After receiving FL, par. meeting criteria received the dosimetric dose (DD), administered 6-8 weeks after the 3rd cycle of FL. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Par. received \>=3 doses (4 drops by mouth \[DBM\], 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 DBM, TID) of Lugol's solution, or KI tablets (130 mg BM, once a day) \>=24 hrs prior to administration of the DD and continued daily for 14 days after the therapeutic dose (TD), administered 7-14 days after the DD. The TD was an IV infusion of 450 mg TST over 1 hr, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.
Overall Study STARTED	2	36
Overall Study COMPLETED	0	20
Overall Study NOT COMPLETED	2	16

Reasons for withdrawal

Measure	Received Less Than 3 Cycles of Fludarabine Participants received less than 3 cycles of intravenous (IV) fludarabine monophosphate (25 milligrams/meter\^2/day \[mg/m\^2/day\]) for 5 days every 5 to 6 weeks.	Fludarabine (3 Cycles); TST and Iodine I 131 TST Participants (par.) received 3 cycles of IV fludarabine (FL) monophosphate (25 mg/m\^2/day) for 5 days every 5-6 weeks. After receiving FL, par. meeting criteria received the dosimetric dose (DD), administered 6-8 weeks after the 3rd cycle of FL. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Par. received \>=3 doses (4 drops by mouth \[DBM\], 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 DBM, TID) of Lugol's solution, or KI tablets (130 mg BM, once a day) \>=24 hrs prior to administration of the DD and continued daily for 14 days after the therapeutic dose (TD), administered 7-14 days after the DD. The TD was an IV infusion of 450 mg TST over 1 hr, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.
Overall Study Lost to Follow-up	1	3
Overall Study Withdrawal by Subject	0	1
Overall Study Progressive Disease	0	11
Overall Study Didn't Meet Criteria for TST/I 131 TST	0	1
Overall Study Co-morbid Illness	1	0

Baseline Characteristics

Study of Safety and Efficacy of a Sequential Regimen Consisting of Three Cycles of Fludarabine Followed by Tositumomab and Iodine I 131 Tositumomab

Baseline characteristics by cohort

Measure	Received Less Than 3 Cycles of Fludarabine n=2 Participants Participants received less than 3 cycles of intravenous (IV) fludarabine monophosphate (25 milligrams/meter\^2/day \[mg/m\^2/day\]) for 5 days every 5 to 6 weeks.	Fludarabine (3 Cycles); TST and Iodine I 131 TST n=36 Participants Participants (par.) received 3 cycles of IV fludarabine (FL) monophosphate (25 mg/m\^2/day) for 5 days every 5-6 weeks. After receiving FL, par. meeting criteria received the dosimetric dose (DD), administered 6-8 weeks after the 3rd cycle of FL. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Par. received \>=3 doses (4 drops by mouth \[DBM\], 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 DBM, TID) of Lugol's solution, or KI tablets (130 mg BM, once a day) \>=24 hrs prior to administration of the DD and continued daily for 14 days after the therapeutic dose (TD), administered 7-14 days after the DD. The TD was an IV infusion of 450 mg TST over 1 hr, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Total n=38 Participants Total of all reporting groups
Age, Continuous	61.0 Years STANDARD_DEVIATION 11.3 • n=5 Participants	51.2 Years STANDARD_DEVIATION 13.4 • n=7 Participants	51.7 Years STANDARD_DEVIATION 13.4 • n=5 Participants
Gender Female	1 Participants n=5 Participants	16 Participants n=7 Participants	17 Participants n=5 Participants
Gender Male	1 Participants n=5 Participants	20 Participants n=7 Participants	21 Participants n=5 Participants
Race/Ethnicity, Customized White	2 participants n=5 Participants	34 participants n=7 Participants	36 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Black	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST dosimetric dose (DD) (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)

Population: Intent-to-Treat (ITT)-Exposed Population: all participants who were enrolled into the study and who received at least 1 dose of fludarabine. The data are presented for the subgroup of the ITT-Exposed Population for those participants who received the dosimetric and therapeutic dose of TST/I 131 TST.

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and does not necessarily have to have a causal relationship (association) with this treatment. Therefore, an AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not it was considered to be related to the medicinal product. Laboratory abnormalities were recorded as AEs only if they were associated with clinical sequelae and/or required an intervention.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=35 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With Any Adverse Event (AE)	33 participants	34 participants	38 participants

PRIMARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)

Population: ITT-Exposed Population

All noxious and unintended responses to a study treatment related to any dose were considered as TRAEs. A response to a study treatment indicates that a causal relationship between a study drug and an adverse event was at least a reasonable possibility, i.e., the relationship cannot be ruled out.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=35 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With Any Treatment-related Adverse Event (TRAE)	32 participants	34 participants	38 participants

PRIMARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)

Population: ITT-Exposed Population

Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=35 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With Any Grade 3 or Grade 4 Adverse Event	17 participants	30 participants	34 participants

PRIMARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)

Population: ITT-Exposed Population

All of the treatment-related grade 3 (severe and undesirable) and grade 4 (life-threatening or disabling) adverse events experienced by the participants were recorded.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=35 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With Any Treatment-related Grade 3 or Grade 4 Adverse Event	16 participants	30 participants	34 participants

PRIMARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)

Population: ITT-Exposed Population

An SAE was defined as any event occurring at any dose that results in any of the following outcomes: death, a life threatening adverse drug experience (at immediate risk of death from the experience as it occurred), inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered to be a serious adverse drug experience when based upon appropriate medical judgment.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=35 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With Any Serious Adverse Event (SAE)	2 participants	7 participants	8 participants

PRIMARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)

Population: ITT-Exposed Population

All of the treatment-related SAEs experienced by the participants were recorded.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=35 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With Any Treatment-related SAE	0 participants	7 participants	7 participants

PRIMARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)

Population: ITT-Exposed Population

AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. mm, millimeters; mm^3, millimeters cubed. Grade 3 and Grade 4 AEs are reported to focus on the most severe AEs.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=35 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Left ventricular dysfunction	1 participants	0 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Myocardial infarction	1 participants	0 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Autoimmune thyroiditis	0 participants	1 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Pyrexia	1 participants	0 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Headache	0 participants	1 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Dyspnoea	1 participants	0 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Absolute neutrophil count <1000 cells/mm^3	11 participants	27 participants	31 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs White blood cell count <2000 cells/mm^3	12 participants	26 participants	30 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Platelet count <50000 cells/mm^3	3 participants	17 participants	19 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Hemoglobin <8.0 grams/deciliter	1 participants	10 participants	11 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Neutropenia	7 participants	2 participants	9 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Anaemia	1 participants	3 participants	4 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Leukopenia	1 participants	3 participants	4 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Thrombocytopenia	1 participants	2 participants	3 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Febrile neutropenia	0 participants	2 participants	2 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Myelodysplastic syndrome	0 participants	2 participants	2 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Acute myeloid leukaemia	0 participants	1 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Chronic myelomonocytic leukaemia	0 participants	1 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Prostate cancer	0 participants	1 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Squamous cell carcinoma	0 participants	1 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Nausea	1 participants	1 participants	2 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Arrhythmia	1 participants	0 participants	1 participants
Number of Participants With the Indicated Grade 3 and Grade 4 AEs Cardiac failure congestive	1 participants	0 participants	1 participants

PRIMARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)

Population: ITT-Exposed Population

All noxious and unintended responses to a study treatment related to any dose were considered as TRAEs. A response to a study treatment indicates that a causal relationship between a study drug and an adverse event was at least a reasonable possibility, i.e., the relationship cannot be ruled out.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=35 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Absolute neutrophil count <1000 cells/mm^3	11 participants	27 participants	31 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen White blood cell count <2000 cells/mm^3	12 participants	26 participants	30 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Platelet count <50000 cells/mm^3	3 participants	17 participants	19 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Hemoglobin <8.0 grams/deciliter	1 participants	10 participants	11 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Fatigue	7 participants	11 participants	16 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Pyrexia	8 participants	10 participants	14 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Asthenia	5 participants	5 participants	9 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Nasopharyngitis	1 participants	3 participants	4 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Chills	3 participants	3 participants	6 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Nausea	12 participants	9 participants	18 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Vomiting	2 participants	5 participants	7 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Rash	6 participants	2 participants	8 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Ecchymosis	1 participants	4 participants	5 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Headache	3 participants	6 participants	8 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Dizziness	0 participants	5 participants	5 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Neutropenia	11 participants	2 participants	12 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Anaemia	2 participants	9 participants	10 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Leukopenia	3 participants	3 participants	5 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Myalgia	1 participants	4 participants	5 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Arthralgia	0 participants	4 participants	4 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Cough	5 participants	10 participants	14 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Nasal congestion	4 participants	6 participants	8 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Dyspnoea	2 participants	5 participants	6 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Oropharyngeal pain	2 participants	4 participants	6 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Rhinorrhoea	2 participants	2 participants	4 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Sinusitis	2 participants	3 participants	5 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Decreased appetite	6 participants	4 participants	10 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Insomnia	2 participants	2 participants	4 participants
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen Palpitations	1 participants	3 participants	4 participants

PRIMARY outcome

Timeframe: Day 1 to Day 730 (24 Months) after receiving the dosimetric dose

Population: ITT-Exposed Population: participants who were evaluable for HAMA (those who did not have a positive HAHA level at Baseline) and those who received dosimetric and therapeutic doses were evaluated.

The administration of murine antibodies may form HAMA. A HAMA assay was performed using the ImmunoSTRIP HAMA IgG enzyme-linked immune absorbent assay by a central laboratory (Covance Classic Laboratory Services, Indianapolis, IN). Fludarabine, a known immunosuppressant, might decrease HAMA production in addition to reducing bone marrow involvement. To be "positive," a participant had to have a positive HAMA assessment at any follow-up visit (Weeks 12 and 25; Months 12, 18, and 24).

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=32 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Study Entry) But Positive or Negative at Weeks 12 and 25 and at Months 12, 18, and 24 Positive	2 participants	—	—
Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Study Entry) But Positive or Negative at Weeks 12 and 25 and at Months 12, 18, and 24 Negative	30 participants	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 730 (24 Months) after receiving the dosimetric dose

Population: ITT-Exposed Population: participants who received dosimetric and therapeutic doses and those who were converted to HAMA positivity were evaluated.

Kaplan-Meier estimates of the time to HAMA positivity (days from the first fludarabine dose) was determined for participants who converted to HAMA positivity.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=2 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Time to HAMA Positivity From the First TST/I 131 TST Dosimetric Dose for the Participants Achieving HAMA Positivity Participant 1	184 days 7.8	—	—
Time to HAMA Positivity From the First TST/I 131 TST Dosimetric Dose for the Participants Achieving HAMA Positivity Participant 2	195 days	—	—

PRIMARY outcome

Timeframe: Baseline (Week -16) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512

Population: ITT-Exposed Population: baseline TSH levels were determined for 36 participants. Of 35 participants who received the dosimetric and therapeutic doses of TST/I-131 TST, 2 had elevated TSH at baseline, and 33 were assessed for developing elevated TSH.

The number of participants with elevated TSH levels is reported. An elevated TSH level indicates that an insufficient amount of the thyroid hormone is being produced. Insufficient thyroid hormone production is known as hypothyroidism. The normal range of TSH is between 0.2 and 6.1 milliunits per liter (mU/L).

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=35 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 286, n=33	0 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 312, n=33	1 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 364, n=33	1 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 416, n=33	0 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 468, n=33	0 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 512, n=33	0 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 52, n=33	1 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 78, n=33	4 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 234, n=33	0 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 260, n=33	0 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 104, n=33	3 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 130, n=33	1 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 156, n=33	0 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 182, n=33	0 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 208, n=33	0 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Baseline (Week -16), n=35	2 participants	—	—
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 Week 25, n=33	3 participants	—	—

PRIMARY outcome

Timeframe: Baseline (study entry; Week -16) and Week 2 to Week 3 (prior to the therapeutic dose)

Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses were evaluated.

Thyroid medication included any prescribed medication for the treatment of thyroid dysfunction.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=35 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With Thyroid Medication Use Prior to the Therapeutic Dose	0 participants	—	—

PRIMARY outcome

Timeframe: up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose)

Population: ITT-Exposed Population: all participants who received the dosimetric dose were evaluated.

Nadir was defined as the lowest laboratory value recorded up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose).

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=35 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Time to Nadir for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets ANC	48 days Interval 36.0 to 90.0	—	—
Time to Nadir for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets Hemoglobin	50 days Interval 28.0 to 87.0	—	—
Time to Nadir for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets Platelets	36 days Interval 22.0 to 48.0	—	—

PRIMARY outcome

Timeframe: up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose)

Population: ITT-Exposed Population: only the 35 participants who received the dosimetric dose were evaluated.

Nadir was defined as the lowest laboratory value recorded up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose).

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=35 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Nadir Values for Absolute Neutrophil Count (ANC)	0.8 10^3/mm^3 Interval 0.0 to 4.0	—	—

PRIMARY outcome

Timeframe: up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose)

Population: ITT-Exposed Population: only the 35 participants who received the dosimetric dose were evaluated.

Nadir was defined as the lowest laboratory value recorded up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose).

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=35 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Nadir Values for Hemoglobin	10.7 g/dL Interval 6.0 to 15.0	—	—

PRIMARY outcome

Timeframe: up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose)

Population: ITT-Exposed Population: only the 35 participants who received the dosimetric dose were evaluated.

Nadir was defined as the lowest laboratory value recorded up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose).

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=35 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Nadir Values for Platelet Count	53 10^3/microliter Interval 4.0 to 126.0	—	—

PRIMARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST dosimetric dose (DD) (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)

Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses were evaluated.

Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades (G): 0=No AE or within normal limits; 1=Mild AE; 2=Moderate AE; 3=Severe and undesirable AE; 4=Life-threatening or disabling AE; 5=Death related to AE. ANC (10^3/mm^3): G1=1.5 to <2.0, G2=1.0 to <1.5, G3=0.5 to < 1.0, G4=<0.5. Hemoglobin (g/dL): G1=10.0 to <12.0, G2=8.0 to <10.0, G3=6.5 to <8.0, G4=< 6.5. Platelets (10^3/microliter): G1=75 to <150, G2=50 to <75, G3=25 to <50, G4=<25.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=35 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With Any Grade 3 or Grade 4 Toxicity (AE) for Hematological Parameters (Absolute Neutrophil Count [ANC], Hemoglobin, and Platelets) ANC	28 participants	—	—
Number of Participants With Any Grade 3 or Grade 4 Toxicity (AE) for Hematological Parameters (Absolute Neutrophil Count [ANC], Hemoglobin, and Platelets) Hemoglobin	10 participants	—	—
Number of Participants With Any Grade 3 or Grade 4 Toxicity (AE) for Hematological Parameters (Absolute Neutrophil Count [ANC], Hemoglobin, and Platelets) Platelets	17 participants	—	—

PRIMARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST dosimetric dose (DD) (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)

Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses were evaluated.

Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades (G): 0=No AE or within normal limits; 1=Mild AE; 2=Moderate AE; 3=Severe and undesirable AE; 4=Life-threatening or disabling AE; 5=Death related to AE. ANC (10^3/mm^3): G1=1.5 to <2.0, G2=1.0 to <1.5, G3=0.5 to < 1.0, G4=<0.5. Hemoglobin (g/dL): G1=10.0 to <12.0, G2=8.0 to <10.0, G3=6.5 to <8.0, G4=< 6.5. Platelets (10^3/microliter): G1=75 to <150, G2=50 to <75, G3=25 to <50, G4=<25.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=35 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Duration of Any Grade 3 or Grade 4 Toxicity for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets ANC	31 days Interval 2.0 to 877.0	—	—
Duration of Any Grade 3 or Grade 4 Toxicity for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets Hemoglobin	16 days Interval 3.0 to 199.0	—	—
Duration of Any Grade 3 or Grade 4 Toxicity for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets Platelets	29 days Interval 2.0 to 83.0	—	—

PRIMARY outcome

Timeframe: Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13)

Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses were evaluated.

An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Colloquially, infections are usually considered to be caused by microscopic organisms or microparasites like viruses, bacteria, and viroids, although larger organisms such as macroparasites and fungi can also infect.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=35 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With Any Infection at Week 16 Post-Fludarabine Treatment and Week 13 Post-TST Treatment Detected by Laboratory Culture of Participant Sample or Investigator Report Week 16 Post-Fludarabine Treatment	11 participants	—	—
Number of Participants With Any Infection at Week 16 Post-Fludarabine Treatment and Week 13 Post-TST Treatment Detected by Laboratory Culture of Participant Sample or Investigator Report Week 13 Post-TST Treatment	9 participants	—	—

PRIMARY outcome

Timeframe: Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13)

Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses and those who had an infection were evaluated. A single participant could have had more than one infection. The number analyzed in the category titles reflects the number of participants who had any infection.

An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Colloquially, infections are usually considered to be caused by microscopic organisms or microparasites like viruses, bacteria, and viroids, although larger organisms such as macroparasites and fungi can also infect.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=11 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of the Indicated Type of Infection Reported by Investigator Based on Laboratory Testing at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment Week 16 Post-Fl treatment, Pneumonia, n=11	1 number of infections	—	—
Number of the Indicated Type of Infection Reported by Investigator Based on Laboratory Testing at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment Week 16 Post-Fl treatment, Other Infections, n=11	12 number of infections	—	—
Number of the Indicated Type of Infection Reported by Investigator Based on Laboratory Testing at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment Week 13 Post-TST Treatment, Pneumonia, n=9	0 number of infections	—	—
Number of the Indicated Type of Infection Reported by Investigator Based on Laboratory Testing at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment Week 13 Post-TST Treatment, Other Infections, n=9	9 number of infections	—	—

PRIMARY outcome

Timeframe: Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13)

Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses and those who had an infection were evaluated.

Specimen samples of the body fluid are cultured for testing whether the infectious organism is present and grown in the culture media to assess the growth pattern of the organisms present in the specimen.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=11 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With a Culture Obtained for Infection at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment Week 16 Post-Fl treatment, n=11	2 participants	—	—
Number of Participants With a Culture Obtained for Infection at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment Week 13 Post-TST Treatment, n=9	1 participants	—	—

PRIMARY outcome

Timeframe: Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13)

Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses, those who had an infection, and from whom the cultures were obtained were evaluated.

The culture results could be positive or negative. The positive culture results indicates that the tested participant have the infection under investigation so therapeutic treatment with anti-infective is required.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=2 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With Positive Culture Results for Infections at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment Week 16 Post-Fl treatment, n=2	0 participants	—	—
Number of Participants With Positive Culture Results for Infections at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment Week 13 Post-TST Treatment, n=1	0 participants	—	—

PRIMARY outcome

Timeframe: Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13)

Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses and those who had an infection were evaluated.

Anti-infectives are capable of acting against infection, by inhibiting the spread of an infectious agent or by killing the infectious agent outright. Anti-infective is a general term that encompasses antibacterials, antibiotics, antifungals, antiprotozoans, and antivirals.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=11 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With an Anti-infective Administered at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment Week 16 Post-Fl treatment, n=11	11 participants	—	—
Number of Participants With an Anti-infective Administered at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment Week 13 Post-TST Treatment, n=9	9 participants	—	—

PRIMARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)

Population: ITT-Exposed Population: two participants who received less than 3 cycles of fludarabine did not receive TST treatment, and hence were not evaluated.

Supportive care involves interventions that help the participants to achieve comfort but do not affect the course of a disease.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=36 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=35 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants Who Received Any Supportive Care After Fludarabine Treatment and After TST Treatment	15 participants	14 participants	—

PRIMARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)

Population: ITT-Exposed Population: two participants who received less than 3 cycles of fludarabine did not receive TST treatment and were not evaluated.

Supportive care involves interventions that help the participants to achieve comfort but do not affect the course of a disease. Supportive care involved administration of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), red blood cell (RBC) transfusions, erythropoietin, and platelet transfusions.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=36 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=35 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment G-CSF/GM-CSF	10 participants	10 participants	—
Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment RBC transfusion	8 participants	7 participants	—
Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment Erythropoietin	7 participants	7 participants	—
Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment Platelet transfusion	3 participants	2 participants	—

SECONDARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)

Population: ITT-Exposed Population. 2 participants (par.) who received \<3 cycles of fludarabine (fl.) did not receive TST treatment and were not evaluated. Par. evaluable for response were those with \>=1 assessment. Three par. were not evaluable for response. None of the responses could be confirmed after fl. treatment; thus, no data are reported for this arm.

CR: Complete resolution of disease-related (DR) radiological abnormalities; disappearance of non-Hodgkin's lymphoma-related signs/symptoms. CCR: Complete resolution of DR symptoms except for residual scar tissue. PR: 50% reduction in the sum of the products of the longest perpendicular diameters of measurable lesions with no new lesions. A confirmed response (resp.) (CR/CCR/PR) had to be confirmed by a consecutive resp. (>=28 days later) that was the same/better. Individual confirmed resp. data only counts that resp. confirmed by the same resp.; not all possible combinations are represented.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=38 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=32 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) n=35 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) Participants with CR, CCR, or PR	0 participants	30 participants	32 participants
Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) Participants with CR or CCR	0 participants	29 participants	29 participants
Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) Participants with PR	0 participants	1 participants	2 participants

SECONDARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)

Population: ITT-Exposed Population. Participants (par.) evaluable for response were those with \>= 1 response assessment. 2 of 38 par. who received \<3 cycles of fludarabine withdrew from the study and were not evaluable for response. 35 of 38 par. received TST and I 131 TST treatment and were evaluated for response.

CR: Complete resolution of disease-related (DR) radiological abnormalities; disappearance of non-Hodgkin's lymphoma-related signs/symptoms. CCR: Complete resolution of DR symptoms except for residual scar tissue. PR: 50% reduction in the sum of the products of the longest perpendicular diameters of measurable lesions with no new lesions.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=36 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=35 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) n=36 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) Participants with CR, CCR, or PR	32 participants	32 participants	36 participants
Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) Participants with CR or CCR	3 participants	30 participants	30 participants
Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) Participants with PR	29 participants	2 participants	6 participants

SECONDARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)

Population: ITT-Exposed Population: participants with confirmed response rates (CR, CCR, or PR) were evaluated.

Progression of disease is defined as a 50% increase from nadir of the sum of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be >2 cm in diameter per radiographic evaluation or >1 cm in diameter by physical examination. All participants without progression of disease were censored.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=30 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=32 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With Progression of Disease Progressed	11 participants	13 participants	—
Number of Participants With Progression of Disease Censored	19 participants	19 participants	—

SECONDARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)

Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses and were classified as responders were evaluated.

Duration of response was defined as the time from the first documented response to the first documented disease progression. Partial Response (PR): 50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions. Responders are the participants with CR, or CCR, or PR.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=30 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=32 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Duration of Response for All Confirmed Responders Participants with CR, CCR, or PR, n=30, 32	NA months The quartiles for duration of response are based on the Kaplan-Meier (KM) method. A median (50% quartile) was not reached because there were not enough events to reach a median on the KM curve.	NA months The quartiles for duration of response are based on the Kaplan-Meier (KM) method. A median (50% quartile) was not reached because there were not enough events to reach a median on the KM curve.	—
Duration of Response for All Confirmed Responders Participants with CR or CCR, n=29, 29	NA months The quartiles for duration of response are based on the Kaplan-Meier (KM) method. A median (50% quartile) was not reached because there were not enough events to reach a median on the KM curve.	NA months The quartiles for duration of response are based on the Kaplan-Meier (KM) method. A median (50% quartile) was not reached because there were not enough events to reach a median on the KM curve.	—
Duration of Response for All Confirmed Responders Participants with PR, n=1, 2	8.1 months The procedure in SAS was not able to calculate the upper or lower limits of the confidence interval.	9.4 months Interval 6.5 to 12.3	—

SECONDARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)

Population: ITT-Exposed Population

PD is defined as a 50% increase from nadir of the sum of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be >2 cm in diameter per radiographic evaluation or >1 cm in diameter by physical examination.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=35 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=38 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With Progressive Disease (PD)	19 participants	21 participants	—

SECONDARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)

Population: ITT-Exposed Population. Participants with disease progression were evaluated.

Time to progression is the time from the treatment start date to the first documented disease progression or death. Disease progression: 50% increase from nadir of the sum of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be >2 cm in diameter per radiographic evaluation or >1 cm in diameter by physical examination.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=19 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=21 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Time to Disease Progression or Death	97.5 months Interval 26.9 to The procedure in SAS was not able to calculate the upper limit of the confidence interval.	95.6 months Interval 30.9 to The procedure in SAS was not able to calculate the upper limit of the confidence interval.	—

SECONDARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)

Population: ITT-Exposed Population

Treatment failure is defined as the occurrence of treatment withdrawal, a decision to seek additional therapy, study removal, progression, alternative therapy for lymphoma, or death.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=35 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=38 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants With a Treatment Failure	20 participants	23 participants	—

SECONDARY outcome

Timeframe: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)

Population: ITT-Exposed Population. Participants with treatment failure were evaluated.

Time to treatment failure is defined as the time from the treatment start date to the first occurrence of treatment withdrawal, a decision to seek additional therapy, study removal, progression, alternative therapy for lymphoma, or death.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=20 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=23 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Time to Treatment Failure	91.4 months Interval 26.3 to The procedure in SAS was not able to calculate the upper limit of the confidence interval.	50.0 months Interval 29.6 to The procedure in SAS was not able to calculate the upper limit of the confidence interval.	—

SECONDARY outcome

Timeframe: Day of TST/I 131 TST dosimetric dose to date of database release (Week 1 to Week 520); First day of fludarabine cycle 1 to date of database release (Week -16 to Week 520)

Population: ITT-Exposed Population

Participants who died during the study period were evaluated for the overall survival endpoint.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=35 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=38 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Number of Participants Who Died During Their Participation in the Study	9 participants	11 participants	—

SECONDARY outcome

Timeframe: Day of TST/I 131 TST dosimetric dose to date of database release (Week 1 to Week 520); First day of fludarabine cycle 1 to date of database release (Week -16 to Week 520)

Population: ITT-Exposed Population

Time to death is defined as the time from the treatment start date to the date of death.

Outcome measures

Measure	Fludarabine/TST and Iodine I 131 TST n=9 Participants Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.	TST and Iodine I 131 TST n=11 Participants The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Time to Death of Participants During Their Participation in the Study	NA months The quartiles for time to death are based on the Kaplan-Meier (KM) method. A median (50% quartile) was not reached because there were not enough events to reach a median on the KM curve.	NA months The quartiles for time to death are based on the Kaplan-Meier (KM) method. A median (50% quartile) was not reached because there were not enough events to reach a median on the KM curve.	—

Adverse Events

Fludarabine

Serious events: 2 serious events

Other events: 33 other events

Deaths: 0 deaths

TST and Iodine I 131 TST

Serious events: 7 serious events

Other events: 34 other events

Deaths: 0 deaths

Fludarabine/TST and Iodine I 131 TST (Combined Regimen)

Serious events: 8 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fludarabine n=38 participants at risk Participants who received any number of cycles of IV fludarabine monophosphate (25 mg/m\^2/day). Each cycle was administered for 5 days every 5 to 6 weeks.	TST and Iodine I 131 TST n=35 participants at risk The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) n=38 participants at risk Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myelomonocytic leukaemia	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Blood and lymphatic system disorders Febrile neutropenia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Cardiac disorders Arrhythmia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Cardiac disorders Cardiac failure congestive	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.

Other adverse events

Measure	Fludarabine n=38 participants at risk Participants who received any number of cycles of IV fludarabine monophosphate (25 mg/m\^2/day). Each cycle was administered for 5 days every 5 to 6 weeks.	TST and Iodine I 131 TST n=35 participants at risk The dosimetric dose (DD) was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Participants received at least 3 doses (4 drops by mouth, 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the therapeutic dose (TD). The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes.	Fludarabine/TST and Iodine I 131 TST (Combined Regimen) n=38 participants at risk Participants received 3 cycles of IV fludarabine monophosphate (25 mg/m\^2/day) for 5 days every 5 to 6 weeks. The DD was administered 6 to 8 weeks after the third cycle of fludarabine. IV administration of unlabeled TST (450 mg) was infused over 1 hr prior to a 30 minute infusion of 35 mg TST trace labeled with 5 mCi iodine I 131. Participants received at least 3 doses (4 drops by mouth, TID) of a saturated solution KI, 3 doses (20 drops by mouth, TID) of Lugol's solution, or KI tablets (130 mg by mouth, once a day) 24 hrs or more prior to administration of the DD and continued daily for 14 days following the TD. The TD was administered 7 to 14 days after the dosimetric dose. The TD was an IV infusion of 450 mg TST over 1 hour, followed by infusion of 35 mg of TST radio labeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 cGy over 20 minutes.
Skin and subcutaneous tissue disorders Hyperhidrosis	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Skin and subcutaneous tissue disorders Pruritus	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Skin and subcutaneous tissue disorders Rash macular	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Blood and lymphatic system disorders Absolute neutrophil count (ANC) <1000 cells/mm^3	28.9% 11/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	77.1% 27/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	81.6% 31/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Blood and lymphatic system disorders White blood cells (WBC) <2000 cells/cmm	31.6% 12/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	74.3% 26/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	78.9% 30/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Blood and lymphatic system disorders Platelets < 50000 cells/mm^3	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	48.6% 17/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	50.0% 19/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Blood and lymphatic system disorders Hemoglobin <8.0 grams/deciliter	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	28.6% 10/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	28.9% 11/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Fatigue	18.4% 7/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	31.4% 11/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	42.1% 16/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Pyrexia	23.7% 9/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	28.6% 10/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	39.5% 15/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Asthenia	13.2% 5/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	14.3% 5/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	23.7% 9/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Chills	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	8.6% 3/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	15.8% 6/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Malaise	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Pain	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Axillary pain	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Chest discomfort	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Feeling abnormal	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Feeling cold	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Feeling hot	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Influenza like illness	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Oedema	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
General disorders Oedema peripheral	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Nausea	34.2% 13/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	28.6% 10/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	47.4% 18/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Vomiting	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	14.3% 5/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	18.4% 7/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Constipation	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Abdominal distension	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Diarrhoea	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Mouth ulceration	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Abdominal pain	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Abdominal pain lower	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Abdominal pain upper	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Dyspepsia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Dysphagia	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Eructation	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Gingival bleeding	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Haemorrhoids	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Lip swelling	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Mouth haemorrhage	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Oral pain	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Retching	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Tongue coated	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Gastrointestinal disorders Toothache	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Skin and subcutaneous tissue disorders Rash	18.4% 7/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	21.1% 8/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Skin and subcutaneous tissue disorders Ecchymosis	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	11.4% 4/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	13.2% 5/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Skin and subcutaneous tissue disorders Drug eruption	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	10.5% 4/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Skin and subcutaneous tissue disorders Night sweats	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Skin and subcutaneous tissue disorders Erythema	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Skin and subcutaneous tissue disorders Urticaria	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Skin and subcutaneous tissue disorders Pain of skin	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Skin and subcutaneous tissue disorders Alopecia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Skin and subcutaneous tissue disorders Dermatitis allergic	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Skin and subcutaneous tissue disorders Photosensitivity reaction	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Nervous system disorders Headache	10.5% 4/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	17.1% 6/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	23.7% 9/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Nervous system disorders Somnolence	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	20.0% 7/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	21.1% 8/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Nervous system disorders Dizziness	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	17.1% 6/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	15.8% 6/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Nervous system disorders Sinus headache	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Nervous system disorders Dysgeusia	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Nervous system disorders Lethargy	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Nervous system disorders Poor quality sleep	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Nervous system disorders Presyncope	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Nervous system disorders Sensory disturbance	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Nervous system disorders Tremor	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Blood and lymphatic system disorders Neutropenia	28.9% 11/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	31.6% 12/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Blood and lymphatic system disorders Anaemia	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	25.7% 9/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	26.3% 10/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Blood and lymphatic system disorders Leukopenia	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	8.6% 3/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	13.2% 5/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Blood and lymphatic system disorders Febrile neutropenia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Blood and lymphatic system disorders Thrombocytopenia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Blood and lymphatic system disorders Pancytopenia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Musculoskeletal and connective tissue disorders Back pain	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	11.4% 4/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	13.2% 5/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Musculoskeletal and connective tissue disorders Myalgia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	11.4% 4/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	13.2% 5/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Musculoskeletal and connective tissue disorders Arthralgia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	11.4% 4/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	10.5% 4/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Musculoskeletal and connective tissue disorders Pain in extremity	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	10.5% 4/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	8.6% 3/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Musculoskeletal and connective tissue disorders Flank pain	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Musculoskeletal and connective tissue disorders Muscular weakness	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Musculoskeletal and connective tissue disorders Pubic pain	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Cough	15.8% 6/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	28.6% 10/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	36.8% 14/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Nasal congestion	13.2% 5/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	17.1% 6/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	21.1% 8/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	14.3% 5/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	18.4% 7/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	14.3% 5/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	15.8% 6/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	10.5% 4/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Rales	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Sinus congestion	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Wheezing	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Tachypnoea	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Infections and infestations Sinusitis	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	8.6% 3/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	13.2% 5/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Infections and infestations Nasopharyngitis	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	8.6% 3/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	10.5% 4/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Infections and infestations Upper respiratory tract infection	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Infections and infestations Herpes zoster	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Infections and infestations Oral herpes	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Infections and infestations Bronchitis	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Infections and infestations Device related infection	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Infections and infestations Herpes virus infection	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Infections and infestations Lower respiratory tract infection	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Infections and infestations Rhinitis	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Metabolism and nutrition disorders Decreased appetite	15.8% 6/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	11.4% 4/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	26.3% 10/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Metabolism and nutrition disorders Hypokalaemia	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Metabolism and nutrition disorders Hypomagnesaemia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Metabolism and nutrition disorders Hyponatraemia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Psychiatric disorders Insomnia	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	10.5% 4/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Psychiatric disorders Anxiety	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	8.6% 3/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Psychiatric disorders Hallucination	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Psychiatric disorders Nightmare	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Cardiac disorders Palpitations	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	8.6% 3/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	10.5% 4/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Cardiac disorders Tachycardia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Cardiac disorders Angina pectoris	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Cardiac disorders Arrhythmia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Cardiac disorders Cardiac failure congestive	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Cardiac disorders Left ventricular dysfunction	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Cardiac disorders Myocardial infarction	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.7% 2/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myelomonocytic leukaemia	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Nervous system disorders Squamous cell carcinoma	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Reproductive system and breast disorders Amenorrhoea	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Reproductive system and breast disorders Benign prostatic hyperplasi	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Reproductive system and breast disorders Menstrual disorder	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Reproductive system and breast disorders Pelvic pain	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Reproductive system and breast disorders Vulvovaginal discomfort	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Vascular disorders Hypotension	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Vascular disorders Hot flush	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Vascular disorders Pallor	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Vascular disorders Varicose vein	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	28.9% 11/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Endocrine disorders Hypothyroidism	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	8.6% 3/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Endocrine disorders Autoimmune thyroiditis	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Renal and urinary disorders Micturition urgency	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Renal and urinary disorders Azotaemia	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Renal and urinary disorders Cystitis noninfective	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Renal and urinary disorders Dysuria	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Renal and urinary disorders Pollakiuria	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Renal and urinary disorders Urinary hesitation	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Ear and labyrinth disorders Ear discomfort	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Ear and labyrinth disorders Ear disorder	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Ear and labyrinth disorders Hypoacusis	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Ear and labyrinth disorders Tinnitus	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Immune system disorders Drug hypersensitivity	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Injury, poisoning and procedural complications Contusion	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	8.6% 3/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	7.9% 3/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Investigations Blood pressure systolic decreased	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Investigations Heart rate increased	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Investigations Weight decreased	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Eye disorders Eye irritation	0.00% 0/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Eye disorders Eye pruritus	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	0.00% 0/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.
Surgical and medical procedures Sinus operation	2.6% 1/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	2.9% 1/35 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.	5.3% 2/38 • All serious and non-serious adverse events (AEs) were reported up to Week 12 after the therapeutic dose. Thereafter, only AEs considered by the investigator to be possibly or probably associated with study treatment were required to be reported.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER