Trial Outcomes & Findings for PF-04856884 (CVX-060) In Combination With Axitinib In Patients With Previously Treated Metastatic Renal Cell Carcinoma (NCT NCT01441414)

NCT ID: NCT01441414

Last Updated: 2019-01-08

Results Overview

Incidence and severity of all treatment-emergent AEs (TEAEs) of both all-causality and treatment-related by preferred term (PT) categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades reported in ≥2 participants overall (CTCAE Grades 3, 4 and 5, combined) for any PT are presented. Participants who are included under all-causality TEAE PT are coded as NA if they appear for the same PT under treatment-related TEAE below. Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 18 participants
• Primary outcome timeframe: 4 months
• Results posted on: 2019-01-08

Participant Flow

This multicenter, open-label study consisted of a safety lead in stage (Part I) followed by a randomized Phase 2 stage (Part II). A total of 18 participants were screened and assigned to treatment in Part I, with 3 participants completing Part I of the study. At the completion of Part I, all 18 participants had discontinued combined treatment.

During Part I, 3 to 4 participants were initially treated with the study drug combination in 28-day cycles. If no participants experienced Cycle 1 dose limiting toxicities (DLTs), another 6 to 9 participants were treated at this dose level. Part II of the study was to be initiated if Cycle 1 DLTs were observed in <33% in at least 12 participants.

Participant milestones

Measure	PF-04856884 + AG-013736 Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice a day. Following the decision of 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).
Overall Study STARTED	18
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Measure	PF-04856884 + AG-013736 Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice a day. Following the decision of 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).
Overall Study Participant died	9
Overall Study Other reasons	3
Overall Study Study terminated by sponsor	2
Overall Study Subject refused further follow-up	1

Baseline Characteristics

PF-04856884 (CVX-060) In Combination With Axitinib In Patients With Previously Treated Metastatic Renal Cell Carcinoma

Baseline characteristics by cohort

Measure	PF-04856884 + AG-013736 n=18 Participants Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice a day. Following the decision of 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).
Age, Continuous	63.2 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 months

Population: The FA set was the primary population for evaluating all safety and efficacy endpoints per the treatment randomization as well as participant characteristics.

Incidence and severity of all treatment-emergent AEs (TEAEs) of both all-causality and treatment-related by preferred term (PT) categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades reported in ≥2 participants overall (CTCAE Grades 3, 4 and 5, combined) for any PT are presented. Participants who are included under all-causality TEAE PT are coded as NA if they appear for the same PT under treatment-related TEAE below.

Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).

Outcome measures

Measure	All-causality CTCAE Grade 3 n=18 Participants Incidence and severity of all-causality CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 4 n=18 Participants Incidence and severity of all-causality CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 5 n=18 Participants Incidence and severity of all-causality CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 3 n=18 Participants Incidence and severity of treatment-related CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 4 n=18 Participants Incidence and severity of treatment-related CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 5 n=18 Participants Incidence and severity of treatment-related CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality Overall n=18 Participants Incidence and severity of all-causality CTCAE Grades 3, 4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related Overall n=18 Participants Incidence and severity of treatment-related CTCAE Grades 3,4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Vision blurred	0 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Diarrhoea	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	10 participants	9 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Pleural effusion	1 participants	0 participants	0 participants	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	3 participants	NA participants participant appears for the same preferred term under all-causality TEAE.
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Anaemia	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	4 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Leukocytosis	2 participants	0 participants	0 participants	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	2 participants	NA participants participant appears for the same preferred term under all-causality TEAE.
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Pericardial effusion	0 participants	1 participants	0 participants	0 participants	1 participants	0 participants	2 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Hyperthyroidism	0 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	2 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Hypothyroidism	0 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Abdominal pain	1 participants	0 participants	0 participants	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	2 participants	NA participants participant appears for the same preferred term under all-causality TEAE.
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Constipation	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	8 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Dry mouth	0 participants	0 participants	0 participants	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	3 participants	NA participants participant appears for the same preferred term under all-causality TEAE.
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Gastritis	0 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	2 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Nausea	1 participants	0 participants	0 participants	1 participants	0 participants	0 participants	11 participants	7 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Oral pain	0 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	2 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Stomatitis	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	2 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Toothache	0 participants	0 participants	0 participants	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	2 participants	NA participants participant appears for the same preferred term under all-causality TEAE.
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Vomiting	1 participants	0 participants	0 participants	1 participants	0 participants	0 participants	10 participants	6 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Asthenia	1 participants	0 participants	0 participants	1 participants	0 participants	0 participants	2 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Fatigue	5 participants	0 participants	0 participants	4 participants	0 participants	0 participants	11 participants	8 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Oedema peripheral	0 participants	0 participants	0 participants	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Pneumonia	1 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	2 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Upper respiratory tract infection	0 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	2 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Urinary tract infection	1 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	3 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Blood creatinine increased	0 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	3 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Weight decreased	2 participants	0 participants	0 participants	1 participants	0 participants	0 participants	4 participants	4 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Decreased appetite	1 participants	0 participants	0 participants	1 participants	0 participants	0 participants	12 participants	11 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Dehydration	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	3 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Hypercalcaemia	0 participants	0 participants	0 participants	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	2 participants	NA participants participant appears for the same preferred term under all-causality TEAE.
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Hypokalaemia	1 participants	0 participants	0 participants	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	2 participants	NA participants participant appears for the same preferred term under all-causality TEAE.
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Hyponatraemia	1 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	2 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Hypovolaemia	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	2 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Arthralgia	1 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	3 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Back pain	1 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	5 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Muscle spasms	0 participants	0 participants	0 participants	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	2 participants	NA participants participant appears for the same preferred term under all-causality TEAE.
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Muscular weakness	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	2 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Myalgia	0 participants	0 participants	0 participants	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	2 participants	NA participants participant appears for the same preferred term under all-causality TEAE.
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Cerebrovascular accident	1 participants	1 participants	0 participants	1 participants	1 participants	0 participants	2 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Dizziness	0 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	4 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Headache	1 participants	0 participants	0 participants	1 participants	0 participants	0 participants	3 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Migraine	1 participants	0 participants	0 participants	1 participants	0 participants	0 participants	2 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Neuropathy peripheral	1 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	2 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Depression	1 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	3 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Insomnia	1 participants	0 participants	0 participants	1 participants	0 participants	0 participants	7 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Proteinuria	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	3 participants	3 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Cough	0 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	7 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Dysphonia	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	5 participants	5 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Dyspnoea	1 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	6 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Hypoxia	1 participants	0 participants	0 participants	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	2 participants	NA participants participant appears for the same preferred term under all-causality TEAE.
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Pulmonary embolism	1 participants	1 participants	0 participants	1 participants	1 participants	0 participants	2 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Night sweats	0 participants	0 participants	0 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	NA participants less than 2 participants per preferred term for treatment-related TEAE	2 participants	NA participants less than 2 participants per preferred term for treatment-related TEAE
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Palmar-plantar erythrodysaesthesia	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	2 participants	2 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Hot flush	0 participants	0 participants	0 participants	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	3 participants	NA participants participant appears for the same preferred term under all-causality TEAE.
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Hypertension	5 participants	0 participants	0 participants	4 participants	0 participants	0 participants	10 participants	9 participants
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall). Hypotension	1 participants	0 participants	0 participants	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	NA participants participant appears for the same preferred term under all-causality TEAE.	4 participants	NA participants participant appears for the same preferred term under all-causality TEAE.

PRIMARY outcome

Timeframe: 4 months

Population: The FA set was the primary population for evaluating all safety and efficacy endpoints per the treatment randomization as well as participant characteristics.

Incidence and severity of all-causality serious adverse events (SAEs) are presented by PT categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades. Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week). Participants with treatment-related TEAE are coded as NA if they appear for the same preferred term under all-causality TEAE.

Outcome measures

Measure	All-causality CTCAE Grade 3 n=18 Participants Incidence and severity of all-causality CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 4 n=18 Participants Incidence and severity of all-causality CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 5 n=18 Participants Incidence and severity of all-causality CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 3 n=18 Participants Incidence and severity of treatment-related CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 4 Incidence and severity of treatment-related CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 5 Incidence and severity of treatment-related CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality Overall Incidence and severity of all-causality CTCAE Grades 3, 4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related Overall Incidence and severity of treatment-related CTCAE Grades 3,4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.
Number of Participants With Serious Adverse Events (SAEs) in Part I Hypertension	0 participants	1 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Pneumonia	1 participants	1 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Pleural effusion	1 participants	1 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Ileus	1 participants	0 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Abdominal pain	0 participants	1 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Ascites	1 participants	0 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Lung infection	0 participants	1 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Back pain	0 participants	1 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Musculoskeletal chest pain	0 participants	1 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Convulsion	1 participants	0 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Embolism	1 participants	0 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Hyponatraemia	0 participants	1 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Dyspnoea	0 participants	1 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Hypotension	0 participants	1 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Cerebrovascular accident	0 participants	1 participants	1 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Migraine	0 participants	1 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Meningioma	0 participants	1 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Hypovolaemia	1 participants	0 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Pulmonary embolism	0 participants	1 participants	1 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Pericardial effusion	0 participants	0 participants	1 participants	0 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Gastrointestinal disorder	0 participants	0 participants	0 participants	1 participants	—	—	—	—
Number of Participants With Serious Adverse Events (SAEs) in Part I Chest discomfort	0 participants	1 participants	0 participants	0 participants	—	—	—	—

PRIMARY outcome

Timeframe: 3 years

Population: The primary efficacy endpoint of estimating median PFS in Part II was not assessed due to early termination of the study.

PFS is defined as the time (in days) from date of randomization to first documentation of investigator assessed tumor progression or death, whichever comes first. Progression free survival was to be calculated as (first event date - the date of randomization +1).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3 years

Population: This endpoint was not assessed due to the early termination of the study.

Incidence and severity of all-causality AEs and SAEs to be presented by PT categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades. Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 months

Population: The FA set was the primary population for evaluating all safety and efficacy endpoints per the treatment randomization as well as participant characteristics.

ORR is defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST), relative to all randomized participants as defined in the FA Set. Confirmed responses are those that persist on repeat imaging study ≥ 4 weeks after initial documentation of response. Participants who do not have on-study radiographic tumor evaluation or who die, progress, or drop out for any reason prior to reaching a CR or PR will be counted as non-responders (NR) in the assessment of ORR.

Outcome measures

Measure	All-causality CTCAE Grade 3 n=18 Participants Incidence and severity of all-causality CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 4 Incidence and severity of all-causality CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 5 Incidence and severity of all-causality CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 3 Incidence and severity of treatment-related CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 4 Incidence and severity of treatment-related CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 5 Incidence and severity of treatment-related CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality Overall Incidence and severity of all-causality CTCAE Grades 3, 4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related Overall Incidence and severity of treatment-related CTCAE Grades 3,4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.
Overall Response Rate (ORR) in Metastatic Renal Cell Cancer (mRCC) Patients Treated With PF-04856884 in Combination With AG-013736 vs. AG-013736 Alone. Complete response (CR)	0 Percentage of participants	—	—	—	—	—	—	—
Overall Response Rate (ORR) in Metastatic Renal Cell Cancer (mRCC) Patients Treated With PF-04856884 in Combination With AG-013736 vs. AG-013736 Alone. Partial response (PR)	11.1 Percentage of participants	—	—	—	—	—	—	—
Overall Response Rate (ORR) in Metastatic Renal Cell Cancer (mRCC) Patients Treated With PF-04856884 in Combination With AG-013736 vs. AG-013736 Alone. ORR (CR + PR)	11.1 Percentage of participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 3 years

Population: This endpoint was not assessed due to the early termination of the study.

DR is defined as the time from the first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of tumor progression or to death due to cancer. Duration of tumor response was to be calculated as (the end date for DR - first CR or PR that is subsequently confirmed +1).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment

Population: The FA set was the primary population for evaluating all safety and efficacy endpoints per the treatment randomization as well as participant characteristics.

Pharmacokinetic parameter, Tmax (Time when maximum serum PF-04856884 concentration was reached) was done using non-compartmental methods.

Outcome measures

Measure	All-causality CTCAE Grade 3 n=18 Participants Incidence and severity of all-causality CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 4 Incidence and severity of all-causality CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 5 Incidence and severity of all-causality CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 3 Incidence and severity of treatment-related CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 4 Incidence and severity of treatment-related CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 5 Incidence and severity of treatment-related CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality Overall Incidence and severity of all-causality CTCAE Grades 3, 4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related Overall Incidence and severity of treatment-related CTCAE Grades 3,4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.
Tmax (Time When Maximum Serum PF-04856884 Concentration Was Reached) CYCLE1/DAY1	2.000 hr Standard Deviation 1.6450	—	—	—	—	—	—	—
Tmax (Time When Maximum Serum PF-04856884 Concentration Was Reached) CYCLE1/DAY22	3.000 hr Standard Deviation 2.1122	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment

Population: The FA set was the primary population for evaluating all safety and efficacy endpoints per the treatment randomization as well as participant characteristics.

Pharmacokinetic parameter Cmax (observed peak PF-04856884 serum concentration) was estimated using noncompartmental methods.

Outcome measures

Measure	All-causality CTCAE Grade 3 n=18 Participants Incidence and severity of all-causality CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 4 Incidence and severity of all-causality CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 5 Incidence and severity of all-causality CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 3 Incidence and severity of treatment-related CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 4 Incidence and severity of treatment-related CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 5 Incidence and severity of treatment-related CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality Overall Incidence and severity of all-causality CTCAE Grades 3, 4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related Overall Incidence and severity of treatment-related CTCAE Grades 3,4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.
Cmax (Observed Peak Serum PF-04856884 Concentration) CYCLE1/DAY1	337100 ng/mL Standard Deviation 76245	—	—	—	—	—	—	—
Cmax (Observed Peak Serum PF-04856884 Concentration) CYCLE1/DAY22	531400 ng/mL Standard Deviation 154780	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment

Population: The FA set was the primary population for evaluating all safety and efficacy endpoints per the treatment randomization as well as participant characteristics.

Pharmacokinetic parameter Cmin (trough PF-04856884 serum concentration) was estimated using noncompartmental methods.

Outcome measures

Measure	All-causality CTCAE Grade 3 n=18 Participants Incidence and severity of all-causality CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 4 Incidence and severity of all-causality CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 5 Incidence and severity of all-causality CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 3 Incidence and severity of treatment-related CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 4 Incidence and severity of treatment-related CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 5 Incidence and severity of treatment-related CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality Overall Incidence and severity of all-causality CTCAE Grades 3, 4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related Overall Incidence and severity of treatment-related CTCAE Grades 3,4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.
Cmin (Trough PF-04856884 Serum Concentration) CYCLE1/DAY1	932.7 ng/mL Standard Deviation 3499.1	—	—	—	—	—	—	—
Cmin (Trough PF-04856884 Serum Concentration) CYCLE1/DAY22	168900 ng/mL Standard Deviation 84507	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 0 and 360 hours post dose and end of study

Population: The FA set was the primary population for evaluating all safety and efficacy endpoints per the treatment randomization as well as participant characteristics.

Detection of neutralizing anti-PF-04856884 antibodies was based on the ability of anti-PF-04856884 neutralizing antibodies to bind to Tag-PF-04856884.

Outcome measures

Measure	All-causality CTCAE Grade 3 n=91 ADA samples Incidence and severity of all-causality CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 4 Incidence and severity of all-causality CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality CTCAE Grade 5 Incidence and severity of all-causality CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 3 Incidence and severity of treatment-related CTCAE Grade 3 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 4 Incidence and severity of treatment-related CTCAE Grade 4 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related CTCAE Grade 5 Incidence and severity of treatment-related CTCAE Grade 5 TEAEs are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	All-causality Overall Incidence and severity of all-causality CTCAE Grades 3, 4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.	Treatment-related Overall Incidence and severity of treatment-related CTCAE Grades 3,4, and 5 are presented. Participants with multiple occurrences of an AE within a category were counted once within the category.
Number of Anti-drug Antibodies (ADA) Samples Confirmed Positive	8 ADA samples	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 3 years

Population: This endpoint of estimating median PFS was not assessed due to early termination of the study.

PFS is defined as the time (in days) from date of randomization to first documentation of investigator assessed tumor progression or death, whichever comes first. PFS was to be calculated as (first event date - the date of randomization +1).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 5 years

Population: This endpoint was not assessed due to the early termination of the study.

OS is defined as the time from the first dose date to date of death. For participants not expiring, their survival times will be censored at the last date they are known to be alive, or 2 year whichever is earlier. The 2-year OS rate will be estimated from a time-to event analysis of OS.

Outcome measures

Outcome data not reported

Adverse Events

PF-04856884 + AG-013736

Serious events: 12 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	PF-04856884 + AG-013736 n=18 participants at risk Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice a day. Following the decision of 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).
Cardiac disorders Pericardial effusion	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Ascites	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal disorder	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Ileus	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Chest discomfort	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Lung infection	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyponatraemia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypovolaemia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebrovascular accident	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Convulsion	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Migraine	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Embolism	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypertension	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypotension	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Other adverse events

Measure	PF-04856884 + AG-013736 n=18 participants at risk Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice a day. Following the decision of 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).
Blood and lymphatic system disorders Anaemia	22.2% 4/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Leukocytosis	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Thrombocytopenia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Angina pectoris	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Pericardial effusion	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Sinus tachycardia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Tinnitus	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Endocrine disorders Hyperthyroidism	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Endocrine disorders Hypothyroidism	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Eye disorders Eye pain	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Eye disorders Vision blurred	16.7% 3/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Eye disorders Visual impairment	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Eye disorders Vitreous floaters	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal discomfort	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal distension	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Aphthous stomatitis	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Ascites	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	44.4% 8/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	55.6% 10/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dry mouth	16.7% 3/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Eructation	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Faecal incontinence	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastritis	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Glossodynia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	61.1% 11/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Oral pain	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Stomatitis	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Toothache	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	55.6% 10/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Asthenia	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Chills	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	61.1% 11/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Inflammation	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Localised oedema	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Mucosal inflammation	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Oedema	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	27.8% 5/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Pain	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholecystitis	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic cyst	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Immune system disorders Hypersensitivity	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Immune system disorders Seasonal allergy	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Bronchitis	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Bronchopulmonary aspergillosis	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Candida infection	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Cellulitis	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Cystitis	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Ear infection	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Herpes zoster	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Otitis media	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Peritonitis	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Tooth infection	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	16.7% 3/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Procedural pain	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Tooth fracture	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Blood creatinine increased	16.7% 3/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Blood thyroid stimulating hormone increased	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Coagulation time prolonged	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Haptoglobin increased	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Neutrophil count abnormal	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Weight decreased	22.2% 4/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations White blood cell count abnormal	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Decreased appetite	66.7% 12/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dehydration	16.7% 3/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypercalcaemia	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypercholesterolaemia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyperglycaemia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypoalbuminaemia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypocalcaemia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypoglycaemia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypokalaemia	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypomagnesaemia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyponatraemia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypophosphataemia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypovolaemia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 3/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	27.8% 5/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Groin pain	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Muscle spasms	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Muscular weakness	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Myalgia	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Neck pain	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Pain in jaw	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cognitive disorder	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Depressed level of consciousness	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	22.2% 4/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dysgeusia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	16.7% 3/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Hypoaesthesia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Lethargy	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Memory impairment	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Migraine	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Neuropathy peripheral	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Somnolence	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Syncope	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Anxiety	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Confusional state	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression	16.7% 3/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Flat affect	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Insomnia	38.9% 7/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Restlessness	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Sleep disorder	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Nocturia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Proteinuria	16.7% 3/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Urinary retention	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Benign prostatic hyperplasia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Scrotal oedema	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	38.9% 7/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dysphonia	27.8% 5/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 6/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Hypoxia	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Rhinalgia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Erythema	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Nail disorder	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Night sweats	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Onychalgia	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	11.1% 2/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Pruritus	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Skin disorder	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Urticaria	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Embolism	5.6% 1/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Hot flush	16.7% 3/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypertension	50.0% 9/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypotension	22.2% 4/18 • From the day the first dose of the investigational product was administered up to 1 year. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 1-800-718-1021

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Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER