Study Of CP-751,871 In Combination With Exemestane In Postmenopausal Women With Hormone Receptor Positive Advanced Breast Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00372996
• Collaborator: (none)
• Enrollment: 219
• Locations: 63
• Arms: 2
• Duration (Months): 88
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To test the efficacy of CP-751,871 combined with exemestane in the treatment of postmenopausal patients with hormone positive advanced breast cancer

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Drug: CP-751,871; Drug: exemestane; Drug: exemestane; Drug: Fulvestrant	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 219 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Two-arm Randomized Open Label Phase 2 Study Of Cp-751,871 In Combination With Exemestane Versus Exemestane Alone As First Line Treatment For Postmenopausal Patients With Hormone Receptor Positive Advanced Breast Cancer
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 CP-751,871 + exemestane Treatment until progression or toxicity	Drug: CP-751,871; CP-751,871 given at 20 mg/kg IV on day 1 of each 21 day cycle.; Drug: exemestane; Exemestane given at 25 mg orally once a day.; Drug: Fulvestrant; Used for salvage therapy and administered according to the local label and standard clinical practice.
Active Comparator: 2	Drug: exemestane; Exemestane given at 25 mg orally once a day. Treatment until progression or toxicity

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [Baseline, Day 1 of Cycles 2 and 4 and then Day 1 of every 3rd cycle starting at Cycle 7 up to 60 months]

   PFS was calculated from the time of randomization to either progression of disease, death, or treatment discontinuation because of unsatisfactory therapy results (such as global deterioration of health status). Disease progression was defined as 1 or more of the following: radiographic progression (20 percent [%] increase in measurable lesions, appearance of new lesions or unequivocal progression of evaluable lesions as defined by Response Evaluation Criteria in Solid Tumors [RECIST]); occurrence of new pleural/pericardial effusions or ascites confirmed by positive cytology; persistent hypercalcemia requiring more than 2 IV treatments with bisphosphonates; intervention for any cancer-related events (radiations, surgery) or new symptoms related to tumor growth requiring participant discontinuation; development of brain metastasis; or death for any cause. Median PFS was estimated from the Kaplan-Meier curve. 95% confidence interval (CI) is based on the Brookmeyer and Crowley method.

2. PFS in Participants With Hemoglobin A1c (HbA1c) Less Than (<) 5.7% at Baseline [Baseline, Day 1 of Cycles 2 and 4 and then Day 1 of every 3rd cycle starting at Cycle 7 up to 60 months]

   PFS was calculated from the time of randomization to either progression of disease, death, or treatment discontinuation because of unsatisfactory therapy results (such as global deterioration of health status). Disease progression was defined as 1 or more of the following: radiographic progression (20% increase in measurable lesions, appearance of new lesions or unequivocal progression of evaluable lesions as defined by RECIST); occurrence of new pleural/pericardial effusions or ascites confirmed by positive cytology; persistent hypercalcemia requiring more than 2 IV treatments with bisphosphonates; intervention for any cancer-related events (radiations, surgery) or new symptoms related to tumor growth requiring participant discontinuation; development of brain metastasis; or death for any cause. Median PFS was estimated from the Kaplan-Meier curve. 95% CI is based on the Brookmeyer and Crowley method.

Secondary Outcome Measures

1. Percentage of Participants Achieving Complete Response (CR), Partial Response (PR), or Stable Disease (SD) Maintained for at Least 6 Months [Baseline, Day 1 of Cycles 2 and 4 and then Day 1 of every 3rd cycle starting at Cycle 7 up to 60 months]

   Objective responses were defined using RECIST as CR: disappearance of all target and nontarget lesions. PR: at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. Nontarget lesions may persist provided there is no unequivocal progression in these lesions. SD: measurements demonstrating neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as progressive disease (PD) during the first 6 weeks after the start of treatment taking as reference the smallest sum LD since the treatment started. During this time, nontarget lesions may persist provided there is no unequivocal progression in these lesions.

2. Maximum Plasma Concentration of CP-751,871 [Predose on Day 1 at Cycles 1, 2, 4, and 5 and 150 days post last dose of CP-751,871 and for salvage therapy, at Day 1 and 150 days post last dose of CP-751,871]

3. Minimum Plasma Concentration of CP-751,871 [Predose on Day 1 at Cycles 1, 2, 4, and 5 and 150 days post last dose of CP-751,871 and for salvage therapy, at Day 1 and 150 days post last dose of CP-751,871]

4. Area Under the Concentration Time Curve From Time 0 to the Last Time Point With Quantifiable Concentration [Predose on Day 1 at Cycles 1, 2, 4, and 5 and 150 days post last dose of CP-751,871 and for salvage therapy, at Day 1 and 150 days post last dose of CP-751,871]

5. Number of Participants With Negative Human Anti-Human Antibodies (HAHAs) [Predose on Day 1 of Cycle 1 and at 150 days post last CP-751,871 infusion]

   Negative human anti-human antibodies were defined as <6.64

6. Percentage of Participants With Circulating Tumor Cells Expressing Insulin-Like Growth Factor 1 Receptor (IGF-IR) [Predose on Day 1 of Cycle 1]

7. Percentage of Participants With Serum Markers Relevant to the IGF-1R Pathway [Predose on Day 1 of Cycles 1 and 4 and at end of treatment prior to beginning salvage therapy]

8. European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire 30 (QLQ-C30) Scores [Predose on Day 1 of each cycle, at the end of treatment and at follow-up, up to 60 months]

   EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score equals (=) better level of functioning or greater degree of symptoms.

9. EORTC QLQ Breast Cancer Module (BR23) Scores [Predose on Day 1, at end of treatment, and at Follow-up, up to 60 months]

   EORTC-QLQ-BR23: included functional scales (body image, sexual functioning, sexual enjoyment, and future perspective) and single item symptoms scales (systemic therapy side effects, breast symptoms, arm symptoms, and upset by hair loss). Questions used 4-point Likert scale (1 ‘Not at All’ to 4 ‘Very Much’). Scores averaged and transformed to 0-100 scale. High score for functional scale=high/healthy level of functioning. High score for single item=high level of symptomatology/problems. Change from baseline=Cycle/Day score minus baseline score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Postmenopausal women with a diagnosis of hormone receptor positive advanced breast cancer

• HbA1c <5.7%

Exclusion Criteria:

• Previous treatment for advanced disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD Medical Center - La Jolla	La Jolla	California	United States	92037
2	UCSD Moores Cancer Center	La Jolla	California	United States	92093
3	UCSD Medical Center - Hillcrest	San Diego	California	United States	92103
4	Washington Cancer Institute (WCI) at Washington Hospital Center (WHC)	Washington	District of Columbia	United States	20010-3017
5	Florida Cancer Research Institute	Davie	Florida	United States	33328
6	Florida Cancer Research Institute	Plantation	Florida	United States	33324
7	Central Baptist Hospital	Lexington	Kentucky	United States	40503
8	Lexington Oncology Associates	Lexington	Kentucky	United States	40503
9	Bluegrass Hematology/Oncology, PSC	Lexington	Kentucky	United States	40504
10	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
11	Bringham and Women's Hospital	Boston	Massachusetts	United States	02115
12	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
13	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
14	Dana-Farber Cancer Institute (DFCI)	Boston	Massachusetts	United States	02215
15	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	2215
16	University of Minnesota Medical Center-Fairview, Riverside Campus	Minneapolis	Minnesota	United States	55454
17	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
18	University Of Minnesota Medical Center	Minneapolis	Minnesota	United States	55455
19	Alamance Regional Medical Center - Cancer Center	Burlington	North Carolina	United States	27215-8700
20	Duke University Medical Center - Morris Cancer Center Clinics	Durham	North Carolina	United States	27710
21	Duke University Medical Center- Department of Medicine Oncology	Durham	North Carolina	United States	27710
22	Duke University Medical Center-Duke Cancer Center	Durham	North Carolina	United States	27710
23	Duke University Medical Center	Durham	North Carolina	United States	27710
24	Duke University School Of Medicine	Durham	North Carolina	United States	27710
25	Texas Oncology - PA Collins Building 5th Floor	Dallas	Texas	United States	75246-2006
26	Baylor College Of Medicine (Bcm)	Houston	Texas	United States	77030
27	Baylor College of Medicine Breast Center	Houston	Texas	United States	77030
28	Fletcher Allen Healthcare	Burlington	Vermont	United States	05401-1473
29	Fletcher Allen Health Care	Burlington	Vermont	United States	05401
30	Fletcher Allen Hospital MCHV Campus	Burlington	Vermont	United States	05401
31	Pharmacist, Investigational Drug Service	Burlington	Vermont	United States	05401
32	Fletcher Allen Healthcare	Burlington	Vermont	United States	05405
33	Fletcher Allan Health Care	Burlington	Vermont	United States	5401
34	Policlinica Privada Site La Plata S.A.	La Plata	Buenos Aires	Argentina	B1902 CMV
35	Breast Clinica de la Mama	La Plata	Buenos Aires	Argentina	B1902CMV
36	Policlinica Privada Site	La Plata	Buenos Aires	Argentina	B1902CMV
37	Policlinica Privada Site La Plata S. A.	La Plata	Buenos Aires	Argentina
38	Instituto de Investigaciones Clinicas	Rosario	Santa Fe	Argentina	S2000CVD
39	Centro Oncologico Rosario	Rosario	Santa Fe	Argentina	S2000DSK
40	Centro Oncologico De Rosario	Rosario	Santa Fe	Argentina	S2000KZE
41	Centro Oncologico	Rosario	Santa Fé	Argentina	S2000KZE
42	Hospital Italiano Cordoba	Cordoba		Argentina	X5004BAL
43	UZ Gasthuisberg, Medische Oncologie	Leuven		Belgium	3000
44	UZ Gasthuisberg	Leuven		Belgium	3000
45	Oncologisch Centrum GZA	Wilrijk		Belgium	2610
46	Jewish General Hospital	Montreal	QC	Brazil	H3T 1E2
47	Instituto Nacional de Cancer - HCII	Santo Cristo	Rio de Janeiro	Brazil	RJ 20220-410
48	Hospital Sao Lucas da PUCRS	Porto Alegre	Rio Grande do Sul	Brazil	90610-000
49	Instituto Nacional DO Cancer - INCA	Rio de Janeiro	RJ	Brazil	20560-120
50	Clínica de Oncologia de porto Alegre Sociedade Simples ltda.	Porto Alegre	RS	Brazil	90430-090
51	Hospital Sao Lucas da PUCRS	Porto Alegre	RS	Brazil	90610-000
52	Hospital Das Clinicas Da Faculdade De Medicina Da Universidade De Sao Paulo Instituto Central	Sao Paulo	SP	Brazil	05403-900
53	Centro de Pesquisa em Oncologia - CPO	Porto Alegre		Brazil	90610-000
54	Instituto Nacional do Cancer	Rio De Janeiro		Brazil	RJ 20230 - 130
55	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
56	Sir Mortimer B. Davis - Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
57	Dipartimento di Medicina, Divisione di Oncologia Medica, Istituto Europeo di Oncologia	Milano		Italy	20141
58	Divisione di Oncologia	Napoli		Italy	80131
59	Uo Oncologia Medica 2 Regione Del Veneto Istituto Oncologico Veneto IRCCS Ospedale Busonera	Padova		Italy	35128
60	VU University Medical Center	Amsterdam		Netherlands	1081 HV
61	Malmö University Hospital	Malmo		Sweden	205 02
62	St Mary's Hospital NHS Trust	London		United Kingdom	W2 1NY
63	Imperial College Healthcare NHS Trust - Charing Cross Hospital	London		United Kingdom	W6 8RF

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00372996
• Other Study ID Numbers: A4021004; 2006-005573-21
• First Posted: Sep 7, 2006
• Last Update Posted: Oct 28, 2015
• Last Verified: Oct 1, 2015

• Additional relevant MeSH terms: Breast Neoplasms; Fulvestrant; Exemestane

Study Results

Participant Flow

Arm/Group Title	CP-751,871 Plus (+) Exemestane	CP-751,871 + Exemestane/CP-751,871 + Fulvestrant	Exemestane	Exemestane/CP-751,871 + Exemestane
Arm/Group Description	Participants received CP-751,871 20 milligrams per kilogram (mg/kg) on Day 1 of each 3-week cycle as an intravenous (IV) infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression.	Participants received CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression. Participants who experienced disease progression received salvage therapy with CP-751,871 20 mg/kg on Day 1 of each 4-week cycle in combination with fulvestrant, administered according to the local label and standard clinical practice. Participants continued salvage treatment if safety and clinical benefit were observed for up to a total of 26 cycles or beyond, if there was continued clinical benefit, safety, and tolerability.	Participants received exemestane 25 mg tablets, by mouth, once daily, until disease progression.	Participants received exemestane 25 mg tablets, by mouth, once daily, until disease progression. Participants who experienced disease progression received salvage therapy with CP-751,871 20 mg/kg on Day 1 of each 3-week cycle in combination with exemestane 25 mg tablets, by mouth, once daily, for up to a total of 20 months or beyond if safety and clinical benefit were observed.
Period Title: Overall Study
STARTED	79	36	61	43
COMPLETED	42	22	33	23
NOT COMPLETED	37	14	28	20

Baseline Characteristics

Arm/Group Title	CP-751,871 + Exemestane	Exemestane	Total
Arm/Group Description	Participants received CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression. Participants who experienced disease progression could have received salvage therapy with CP-751,871 20 mg/kg on Day 1 of each 4-week cycle in combination with fulvestrant, administered according to the local label and standard clinical practice. Participants continued salvage treatment if safety and clinical benefit were observed for up to a total of 26 cycles or beyond, if there was continued clinical benefit, safety, and tolerability.	Participants received exemestane 25 mg tablets, by mouth, once daily, until disease progression. Participants who experienced disease progression could have received salvage therapy with CP-751,871 20 mg/kg on Day 1 of each 3-week cycle in combination with exemestane 25 mg tablets, by mouth, once daily, for up to a total of 20 months or beyond if safety and clinical benefit were observed.	Total of all reporting groups
Overall Participants	115	104	219
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.2 (10.77)	62.7 (10.86)	61.9 (10.82)
Sex: Female, Male (Count of Participants)
Female	115 100%	104 100%	219 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was calculated from the time of randomization to either progression of disease, death, or treatment discontinuation because of unsatisfactory therapy results (such as global deterioration of health status). Disease progression was defined as 1 or more of the following: radiographic progression (20 percent [%] increase in measurable lesions, appearance of new lesions or unequivocal progression of evaluable lesions as defined by Response Evaluation Criteria in Solid Tumors [RECIST]); occurrence of new pleural/pericardial effusions or ascites confirmed by positive cytology; persistent hypercalcemia requiring more than 2 IV treatments with bisphosphonates; intervention for any cancer-related events (radiations, surgery) or new symptoms related to tumor growth requiring participant discontinuation; development of brain metastasis; or death for any cause. Median PFS was estimated from the Kaplan-Meier curve. 95% confidence interval (CI) is based on the Brookmeyer and Crowley method.
Time Frame	Baseline, Day 1 of Cycles 2 and 4 and then Day 1 of every 3rd cycle starting at Cycle 7 up to 60 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all enrolled participants; grouped by randomized arm, where the first 10 participants enrolled but not randomly assigned to treatment were not included.

Arm/Group Title	CP-751,871 + Exemestane	Exemestane
Arm/Group Description	Participants were assigned to receive CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression.	Participants were assigned to receive exemestane 25 mg tablets, by mouth, once daily, until disease progression.
Measure Participants	106	103
Median (95% Confidence Interval) [months]	11.0	9.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CP-751,871 + Exemestane, Exemestane
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.560
	Comments
	Method	Log Rank
	Comments	2-sided p-value from an unstratified log-rank text
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.912
	Confidence Interval	(2-Sided) 80%; 0.744 to 1.118
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was based on Cox proportional hazards model.

2. Primary Outcome

Title	PFS in Participants With Hemoglobin A1c (HbA1c) Less Than (<) 5.7% at Baseline
Description	PFS was calculated from the time of randomization to either progression of disease, death, or treatment discontinuation because of unsatisfactory therapy results (such as global deterioration of health status). Disease progression was defined as 1 or more of the following: radiographic progression (20% increase in measurable lesions, appearance of new lesions or unequivocal progression of evaluable lesions as defined by RECIST); occurrence of new pleural/pericardial effusions or ascites confirmed by positive cytology; persistent hypercalcemia requiring more than 2 IV treatments with bisphosphonates; intervention for any cancer-related events (radiations, surgery) or new symptoms related to tumor growth requiring participant discontinuation; development of brain metastasis; or death for any cause. Median PFS was estimated from the Kaplan-Meier curve. 95% CI is based on the Brookmeyer and Crowley method.
Time Frame	Baseline, Day 1 of Cycles 2 and 4 and then Day 1 of every 3rd cycle starting at Cycle 7 up to 60 months

Outcome Measure Data

Analysis Population Description

FAS; only participants with baseline HbA1c <5.7% were included in the analysis.

Arm/Group Title	CP-751,871 + Exemestane	Exemestane
Arm/Group Description	Participants were assigned to receive CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression.	Participants were assigned to receive exemestane 25 mg tablets, by mouth, once daily, until disease progression.
Measure Participants	39	40
Median (95% Confidence Interval) [months]	13.2	9.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CP-751,871 + Exemestane, Exemestane
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.331
	Comments	2-sided p-value from unstratified log-rank test
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.764
	Confidence Interval	(2-Sided) 70%; 0.572 to 1.020
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was based on the Cox proportional hazards model.

3. Secondary Outcome

Title	Percentage of Participants Achieving Complete Response (CR), Partial Response (PR), or Stable Disease (SD) Maintained for at Least 6 Months
Description	Objective responses were defined using RECIST as CR: disappearance of all target and nontarget lesions. PR: at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. Nontarget lesions may persist provided there is no unequivocal progression in these lesions. SD: measurements demonstrating neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as progressive disease (PD) during the first 6 weeks after the start of treatment taking as reference the smallest sum LD since the treatment started. During this time, nontarget lesions may persist provided there is no unequivocal progression in these lesions.
Time Frame	Baseline, Day 1 of Cycles 2 and 4 and then Day 1 of every 3rd cycle starting at Cycle 7 up to 60 months

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	CP-751,871 + Exemestane	Exemestane
Arm/Group Description	Participants were assigned to receive CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression.	Participants were assigned to receive exemestane 25 mg tablets, by mouth, once daily, until disease progression.
Measure Participants	106	103
Number (95% Confidence Interval) [percentage of participants]	68.9 59.9%	64.1 61.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CP-751,871 + Exemestane, Exemestane
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.463
	Comments
	Method	Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.790
	Confidence Interval	(2-Sided) 95%; -8.0 to 17.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Maximum Plasma Concentration of CP-751,871
Time Frame	Predose on Day 1 at Cycles 1, 2, 4, and 5 and 150 days post last dose of CP-751,871 and for salvage therapy, at Day 1 and 150 days post last dose of CP-751,871

Outcome Measure Data

Analysis Population Description

The study was terminated early due to strategic reasons and pharmacokinetic (PK) sampling was discontinued by Protocol Amendment 6. Therefore, the analysis was not performed and an incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading.

Arm/Group Title	CP-751,871 + Exemestane
Arm/Group Description	Participants received CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression.
Measure Participants	0

5. Secondary Outcome

Title	Minimum Plasma Concentration of CP-751,871
Time Frame	Predose on Day 1 at Cycles 1, 2, 4, and 5 and 150 days post last dose of CP-751,871 and for salvage therapy, at Day 1 and 150 days post last dose of CP-751,871

Outcome Measure Data

Analysis Population Description

The study was terminated early due to strategic reasons and PK sampling was discontinued by Protocol Amendment 6. Therefore, the analysis was not performed and an incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading.

Arm/Group Title	CP-751,871 + Exemestane
Arm/Group Description	Participants received CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression.
Measure Participants	0

6. Secondary Outcome

Title	Area Under the Concentration Time Curve From Time 0 to the Last Time Point With Quantifiable Concentration
Time Frame	Predose on Day 1 at Cycles 1, 2, 4, and 5 and 150 days post last dose of CP-751,871 and for salvage therapy, at Day 1 and 150 days post last dose of CP-751,871

Outcome Measure Data

Analysis Population Description

The study was terminated early due to strategic reasons and PK sampling was discontinued by Protocol Amendment 6. Therefore, the analysis was not performed and an incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading.

Arm/Group Title	CP-751,871 + Exemestane
Arm/Group Description	Participants received CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression.
Measure Participants	0

7. Secondary Outcome

Title	Number of Participants With Negative Human Anti-Human Antibodies (HAHAs)
Description	Negative human anti-human antibodies were defined as <6.64
Time Frame	Predose on Day 1 of Cycle 1 and at 150 days post last CP-751,871 infusion

Outcome Measure Data

Analysis Population Description

All randomized participants who started treatment and who had at least 1 sample submitted for the biomarker; collection of samples for this analysis was stopped after Amendment 6. All samples were negative to HAHA.

Arm/Group Title	CP-751,871 + Exemestane
Arm/Group Description	Participants received CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression.
Measure Participants	37
Measure samples	66
Number [participants]	37 32.2%

8. Secondary Outcome

Title	Percentage of Participants With Circulating Tumor Cells Expressing Insulin-Like Growth Factor 1 Receptor (IGF-IR)
Time Frame	Predose on Day 1 of Cycle 1

Outcome Measure Data

Analysis Population Description

The study was terminated early due to strategic reasons and biomarker sampling was discontinued by Protocol Amendment 6. Therefore, the analysis was not performed and an incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading.

Arm/Group Title	CP-751,871 + Exemestane	Exemestane
Arm/Group Description	Participants received CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression.	Participants received exemestane 25 mg tablets, by mouth, once daily, until disease progression.
Measure Participants	0	0

9. Secondary Outcome

Title	Percentage of Participants With Serum Markers Relevant to the IGF-1R Pathway
Time Frame	Predose on Day 1 of Cycles 1 and 4 and at end of treatment prior to beginning salvage therapy

Outcome Measure Data

Analysis Population Description

The study was terminated early due to strategic reasons and biomarker sampling was discontinued by Protocol Amendment 6. Therefore, the analysis was not performed and an incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading.

Arm/Group Title	CP-751,871 + Exemestane	Exemestane
Arm/Group Description	Participants received CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression.	Participants received exemestane 25 mg tablets, by mouth, once daily, until disease progression.
Measure Participants	0	0

10. Secondary Outcome

Title	European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire 30 (QLQ-C30) Scores
Description	EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score equals (=) better level of functioning or greater degree of symptoms.
Time Frame	Predose on Day 1 of each cycle, at the end of treatment and at follow-up, up to 60 months

Outcome Measure Data

Analysis Population Description

The study was terminated early secondary to strategic reasons and the questionnaires were discontinued by Protocol Amendment 6. Therefore, the analysis was not performed and an incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading.

Arm/Group Title	CP-751,871 + Exemestane	Exemestane
Arm/Group Description	Participants received CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression.	Participants received exemestane 25 mg tablets, by mouth, once daily, until disease progression.
Measure Participants	0	0

11. Secondary Outcome

Title	EORTC QLQ Breast Cancer Module (BR23) Scores
Description	EORTC-QLQ-BR23: included functional scales (body image, sexual functioning, sexual enjoyment, and future perspective) and single item symptoms scales (systemic therapy side effects, breast symptoms, arm symptoms, and upset by hair loss). Questions used 4-point Likert scale (1 ‘Not at All’ to 4 ‘Very Much’). Scores averaged and transformed to 0-100 scale. High score for functional scale=high/healthy level of functioning. High score for single item=high level of symptomatology/problems. Change from baseline=Cycle/Day score minus baseline score.
Time Frame	Predose on Day 1, at end of treatment, and at Follow-up, up to 60 months

Outcome Measure Data

Analysis Population Description

The study was terminated early secondary to strategic reasons and the questionnaires were discontinued by Protocol Amendment 6. Therefore, the analysis was not performed and an incomplete data set was not reported because it would potentially skew the data, and is not statistically relevant, thus could be misleading.

Arm/Group Title	CP-751,871 + Exemestane	Exemestane
Arm/Group Description	Participants received CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression.	Participants received exemestane 25 mg tablets, by mouth, once daily, until disease progression.
Measure Participants	0	0

Adverse Events

Time Frame	Adverse events (AEs) recorded from informed consent through and including 150 calendar days after the last administration of investigational product. Active reporting period for exemestane/fulvestrant clarified to 28 days after last dose in Amendment 6.
Adverse Event Reporting Description	The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	CP-751,871 + Exemestane		CP-751,871 + Fulvestrant (After CP-751,871+Exemestane)		Exemestane		CP-751,871 + Exemestane (After Exemestane)
Arm/Group Description	Participants received CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression.		Participants received CP-751,871 20 mg/kg on Day 1 of each 3-week cycle as an IV infusion in combination with exemestane 25 mg tablets, by mouth, once daily, until disease progression. Participants who experienced disease progression received salvage therapy with CP-751,871 20 mg/kg on Day 1 of each 4-week cycle in combination with fulvestrant, administered according to the local label and standard clinical practice. Participants continued salvage treatment if safety and clinical benefit were observed for up to a total of 26 cycles or beyond, if there was continued clinical benefit, safety, and tolerability. Adverse events are presented from the period of time when the participant was receiving salvage therapy treatment only.		Participants received exemestane 25 mg tablets, by mouth, once daily, until disease progression.		Participants received exemestane 25 mg tablets, by mouth, once daily, until disease progression. Participants who experienced disease progression received salvage therapy with CP-751,871 20 mg/kg on Day 1 of each 3-week cycle in combination with exemestane 25 mg tablets, by mouth, once daily, for up to a total of 20 months or beyond if safety and clinical benefit were observed. Adverse events are presented from the period of time when the participant was receiving salvage therapy treatment only.
All Cause Mortality
	CP-751,871 + Exemestane		CP-751,871 + Fulvestrant (After CP-751,871+Exemestane)		Exemestane		CP-751,871 + Exemestane (After Exemestane)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	CP-751,871 + Exemestane		CP-751,871 + Fulvestrant (After CP-751,871+Exemestane)		Exemestane		CP-751,871 + Exemestane (After Exemestane)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/115 (33%)		11/36 (30.6%)		23/104 (22.1%)		15/43 (34.9%)
Blood and lymphatic system disorders
Febrile neutropenia	2/115 (1.7%)		0/36 (0%)		2/104 (1.9%)		1/43 (2.3%)
Neutropenia	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Pancytopenia	1/115 (0.9%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Thrombocytopenia	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Cardiac disorders
Cardiac failure	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Endocrine disorders
Hyperthyroidism	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Eye disorders
Cataract	0/115 (0%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Macular fibrosis	1/115 (0.9%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/115 (0%)		0/36 (0%)		0/104 (0%)		1/43 (2.3%)
Abdominal pain	1/115 (0.9%)		1/36 (2.8%)		1/104 (1%)		1/43 (2.3%)
Abdominal rigidity	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Constipation	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Diarrhoea	0/115 (0%)		0/36 (0%)		0/104 (0%)		2/43 (4.7%)
Dysphagia	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Gastric ulcer	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Gastrointestinal toxicity	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Gastrooesophageal reflux disease	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Nausea	1/115 (0.9%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Pancreatitis acute	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Stomatitis	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		1/43 (2.3%)
Vomiting	3/115 (2.6%)		0/36 (0%)		1/104 (1%)		2/43 (4.7%)
General disorders
Asthenia	1/115 (0.9%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Chest pain	1/115 (0.9%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Disease progression	5/115 (4.3%)		2/36 (5.6%)		4/104 (3.8%)		6/43 (14%)
General physical health deterioration	0/115 (0%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Impaired healing	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Malaise	2/115 (1.7%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Mucosal inflammation	1/115 (0.9%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Pain	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Pyrexia	0/115 (0%)		0/36 (0%)		0/104 (0%)		1/43 (2.3%)
Hepatobiliary disorders
Cholelithiasis	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Portal vein thrombosis	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Immune system disorders
Hypersensitivity	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Infections and infestations
Bacteraemia	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Bronchopneumonia	1/115 (0.9%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Clostridium difficile colitis	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Cystitis	2/115 (1.7%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Erysipelas	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Gastrointestinal infection	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Lymphangitis	0/115 (0%)		0/36 (0%)		0/104 (0%)		1/43 (2.3%)
Peritonitis bacterial	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Pneumonia	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Pulmonary sepsis	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Respiratory tract infection	2/115 (1.7%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Sepsis	0/115 (0%)		0/36 (0%)		3/104 (2.9%)		0/43 (0%)
Urinary tract infection	2/115 (1.7%)		0/36 (0%)		2/104 (1.9%)		1/43 (2.3%)
Viral infection	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Injury, poisoning and procedural complications
Craniocerebral injury	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Fall	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		1/43 (2.3%)
Femur fracture	0/115 (0%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Hip fracture	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Humerus fracture	1/115 (0.9%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Radius fracture	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Scapula fracture	0/115 (0%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Spinal compression fracture	0/115 (0%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Subdural haematoma	2/115 (1.7%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Upper limb fracture	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/115 (0.9%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Dehydration	0/115 (0%)		1/36 (2.8%)		2/104 (1.9%)		1/43 (2.3%)
Diabetes mellitus	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Diabetic ketoacidosis	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Hypercalcaemia	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Hyperglycaemia	8/115 (7%)		0/36 (0%)		0/104 (0%)		2/43 (4.7%)
Musculoskeletal and connective tissue disorders
Back pain	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Pain in extremity	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Lung neoplasm malignant	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Lymphangiosis carcinomatosa	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Malignant neoplasm progression	0/115 (0%)		0/36 (0%)		2/104 (1.9%)		0/43 (0%)
Pancreatic carcinoma	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Spinal cord neoplasm	0/115 (0%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Vulval cancer	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Nervous system disorders
Aphasia	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Balance disorder	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Cerebral haemorrhage	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Cerebral ischaemia	0/115 (0%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Cerebrovascular accident	0/115 (0%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Depressed level of consciousness	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Dysarthria	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Grand mal convulsion	2/115 (1.7%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Headache	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Peripheral sensory neuropathy	0/115 (0%)		0/36 (0%)		0/104 (0%)		1/43 (2.3%)
Sensory loss	2/115 (1.7%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Syncope	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Psychiatric disorders
Confusional state	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		1/43 (2.3%)
Insomnia	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Suicidal ideation	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Renal and urinary disorders
Haematuria	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		1/43 (2.3%)
Renal failure	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Renal failure acute	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
Apnoea	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Dyspnoea	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Epistaxis	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Haemoptysis	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Haemothorax	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Organising pneumonia	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Pulmonary embolism	0/115 (0%)		1/36 (2.8%)		2/104 (1.9%)		2/43 (4.7%)
Respiratory failure	0/115 (0%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Skin and subcutaneous tissue disorders
Skin mass	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Surgical and medical procedures
Open reduction of fracture	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Vascular disorders
Deep vein thrombosis	0/115 (0%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Embolism	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Haemorrhage	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Hypertension	1/115 (0.9%)		0/36 (0%)		0/104 (0%)		0/43 (0%)
Venous insufficiency	0/115 (0%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	CP-751,871 + Exemestane		CP-751,871 + Fulvestrant (After CP-751,871+Exemestane)		Exemestane		CP-751,871 + Exemestane (After Exemestane)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	113/115 (98.3%)		34/36 (94.4%)		96/104 (92.3%)		43/43 (100%)
Blood and lymphatic system disorders
Anaemia	8/115 (7%)		3/36 (8.3%)		9/104 (8.7%)		5/43 (11.6%)
Thrombocytopenia	5/115 (4.3%)		2/36 (5.6%)		1/104 (1%)		1/43 (2.3%)
Cardiac disorders
Palpitations	7/115 (6.1%)		1/36 (2.8%)		6/104 (5.8%)		0/43 (0%)
Ear and labyrinth disorders
Deafness	7/115 (6.1%)		2/36 (5.6%)		0/104 (0%)		0/43 (0%)
Ear pain	2/115 (1.7%)		2/36 (5.6%)		0/104 (0%)		0/43 (0%)
Hypoacusis	6/115 (5.2%)		1/36 (2.8%)		0/104 (0%)		0/43 (0%)
Tinnitus	7/115 (6.1%)		0/36 (0%)		2/104 (1.9%)		2/43 (4.7%)
Vertigo	8/115 (7%)		3/36 (8.3%)		2/104 (1.9%)		0/43 (0%)
Eye disorders
Dry eye	7/115 (6.1%)		1/36 (2.8%)		4/104 (3.8%)		1/43 (2.3%)
Eye pain	3/115 (2.6%)		2/36 (5.6%)		0/104 (0%)		1/43 (2.3%)
Lacrimation increased	6/115 (5.2%)		1/36 (2.8%)		3/104 (2.9%)		1/43 (2.3%)
Vision blurred	7/115 (6.1%)		2/36 (5.6%)		1/104 (1%)		1/43 (2.3%)
Gastrointestinal disorders
Abdominal pain	12/115 (10.4%)		3/36 (8.3%)		11/104 (10.6%)		3/43 (7%)
Abdominal pain upper	9/115 (7.8%)		1/36 (2.8%)		6/104 (5.8%)		3/43 (7%)
Constipation	29/115 (25.2%)		8/36 (22.2%)		16/104 (15.4%)		7/43 (16.3%)
Diarrhoea	37/115 (32.2%)		8/36 (22.2%)		22/104 (21.2%)		12/43 (27.9%)
Dry mouth	15/115 (13%)		2/36 (5.6%)		5/104 (4.8%)		5/43 (11.6%)
Dyspepsia	9/115 (7.8%)		4/36 (11.1%)		9/104 (8.7%)		3/43 (7%)
Dysphagia	3/115 (2.6%)		2/36 (5.6%)		0/104 (0%)		1/43 (2.3%)
Gastrooesophageal reflux disease	4/115 (3.5%)		2/36 (5.6%)		1/104 (1%)		2/43 (4.7%)
Haemorrhoids	6/115 (5.2%)		2/36 (5.6%)		2/104 (1.9%)		1/43 (2.3%)
Nausea	35/115 (30.4%)		8/36 (22.2%)		19/104 (18.3%)		15/43 (34.9%)
Stomatitis	8/115 (7%)		4/36 (11.1%)		0/104 (0%)		1/43 (2.3%)
Toothache	10/115 (8.7%)		2/36 (5.6%)		1/104 (1%)		0/43 (0%)
Vomiting	23/115 (20%)		4/36 (11.1%)		6/104 (5.8%)		7/43 (16.3%)
General disorders
Asthenia	17/115 (14.8%)		3/36 (8.3%)		13/104 (12.5%)		8/43 (18.6%)
Chest pain	8/115 (7%)		2/36 (5.6%)		8/104 (7.7%)		1/43 (2.3%)
Fatigue	35/115 (30.4%)		11/36 (30.6%)		33/104 (31.7%)		16/43 (37.2%)
Influenza like illness	6/115 (5.2%)		1/36 (2.8%)		2/104 (1.9%)		0/43 (0%)
Injection site pain	0/115 (0%)		2/36 (5.6%)		0/104 (0%)		0/43 (0%)
Oedema peripheral	5/115 (4.3%)		1/36 (2.8%)		10/104 (9.6%)		3/43 (7%)
Pain	7/115 (6.1%)		2/36 (5.6%)		8/104 (7.7%)		6/43 (14%)
Pyrexia	11/115 (9.6%)		1/36 (2.8%)		5/104 (4.8%)		1/43 (2.3%)
Infections and infestations
Cystitis	6/115 (5.2%)		0/36 (0%)		5/104 (4.8%)		3/43 (7%)
Nasopharyngitis	13/115 (11.3%)		0/36 (0%)		9/104 (8.7%)		0/43 (0%)
Sinusitis	6/115 (5.2%)		1/36 (2.8%)		2/104 (1.9%)		0/43 (0%)
Upper respiratory tract infection	7/115 (6.1%)		0/36 (0%)		7/104 (6.7%)		2/43 (4.7%)
Urinary tract infection	21/115 (18.3%)		3/36 (8.3%)		8/104 (7.7%)		8/43 (18.6%)
Investigations
Alanine aminotransferase increased	9/115 (7.8%)		1/36 (2.8%)		3/104 (2.9%)		0/43 (0%)
Aspartate aminotransferase increased	6/115 (5.2%)		1/36 (2.8%)		1/104 (1%)		0/43 (0%)
Blood creatinine increased	6/115 (5.2%)		2/36 (5.6%)		1/104 (1%)		2/43 (4.7%)
Gamma-glutamyltransferase increased	15/115 (13%)		3/36 (8.3%)		2/104 (1.9%)		2/43 (4.7%)
Glycosylated haemoglobin increased	0/115 (0%)		0/36 (0%)		1/104 (1%)		3/43 (7%)
Weight decreased	34/115 (29.6%)		10/36 (27.8%)		5/104 (4.8%)		14/43 (32.6%)
Metabolism and nutrition disorders
Decreased appetite	41/115 (35.7%)		13/36 (36.1%)		13/104 (12.5%)		13/43 (30.2%)
Dehydration	1/115 (0.9%)		0/36 (0%)		1/104 (1%)		3/43 (7%)
Hyperglycaemia	50/115 (43.5%)		9/36 (25%)		4/104 (3.8%)		9/43 (20.9%)
Hyperuricaemia	4/115 (3.5%)		0/36 (0%)		0/104 (0%)		3/43 (7%)
Musculoskeletal and connective tissue disorders
Arthralgia	29/115 (25.2%)		10/36 (27.8%)		41/104 (39.4%)		16/43 (37.2%)
Back pain	30/115 (26.1%)		6/36 (16.7%)		18/104 (17.3%)		11/43 (25.6%)
Bone pain	7/115 (6.1%)		3/36 (8.3%)		11/104 (10.6%)		4/43 (9.3%)
Flank pain	5/115 (4.3%)		2/36 (5.6%)		3/104 (2.9%)		3/43 (7%)
Joint stiffness	3/115 (2.6%)		0/36 (0%)		3/104 (2.9%)		3/43 (7%)
Muscle spasms	41/115 (35.7%)		12/36 (33.3%)		4/104 (3.8%)		8/43 (18.6%)
Muscular weakness	6/115 (5.2%)		0/36 (0%)		1/104 (1%)		0/43 (0%)
Musculoskeletal chest pain	7/115 (6.1%)		2/36 (5.6%)		10/104 (9.6%)		7/43 (16.3%)
Musculoskeletal pain	18/115 (15.7%)		5/36 (13.9%)		15/104 (14.4%)		9/43 (20.9%)
Myalgia	11/115 (9.6%)		2/36 (5.6%)		9/104 (8.7%)		9/43 (20.9%)
Neck pain	9/115 (7.8%)		1/36 (2.8%)		7/104 (6.7%)		5/43 (11.6%)
Pain in extremity	19/115 (16.5%)		7/36 (19.4%)		16/104 (15.4%)		8/43 (18.6%)
Pain in jaw	1/115 (0.9%)		2/36 (5.6%)		2/104 (1.9%)		2/43 (4.7%)
Nervous system disorders
Amnesia	3/115 (2.6%)		2/36 (5.6%)		0/104 (0%)		0/43 (0%)
Dizziness	21/115 (18.3%)		3/36 (8.3%)		13/104 (12.5%)		6/43 (14%)
Dysgeusia	21/115 (18.3%)		2/36 (5.6%)		1/104 (1%)		7/43 (16.3%)
Headache	29/115 (25.2%)		7/36 (19.4%)		23/104 (22.1%)		13/43 (30.2%)
Hypoaesthesia	2/115 (1.7%)		4/36 (11.1%)		3/104 (2.9%)		1/43 (2.3%)
Neuropathy peripheral	6/115 (5.2%)		3/36 (8.3%)		5/104 (4.8%)		1/43 (2.3%)
Psychiatric disorders
Anxiety	8/115 (7%)		2/36 (5.6%)		4/104 (3.8%)		3/43 (7%)
Confusional state	7/115 (6.1%)		2/36 (5.6%)		3/104 (2.9%)		2/43 (4.7%)
Depression	13/115 (11.3%)		4/36 (11.1%)		15/104 (14.4%)		12/43 (27.9%)
Insomnia	13/115 (11.3%)		2/36 (5.6%)		15/104 (14.4%)		5/43 (11.6%)
Renal and urinary disorders
Dysuria	11/115 (9.6%)		1/36 (2.8%)		1/104 (1%)		0/43 (0%)
Reproductive system and breast disorders
Breast pain	6/115 (5.2%)		2/36 (5.6%)		10/104 (9.6%)		5/43 (11.6%)
Pelvic pain	4/115 (3.5%)		2/36 (5.6%)		3/104 (2.9%)		1/43 (2.3%)
Vulvovaginal dryness	6/115 (5.2%)		3/36 (8.3%)		3/104 (2.9%)		1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
Cough	23/115 (20%)		4/36 (11.1%)		17/104 (16.3%)		7/43 (16.3%)
Dyspnoea	19/115 (16.5%)		6/36 (16.7%)		14/104 (13.5%)		0/43 (0%)
Dyspnoea exertional	7/115 (6.1%)		0/36 (0%)		2/104 (1.9%)		1/43 (2.3%)
Epistaxis	15/115 (13%)		3/36 (8.3%)		2/104 (1.9%)		1/43 (2.3%)
Oropharyngeal pain	8/115 (7%)		0/36 (0%)		0/104 (0%)		3/43 (7%)
Skin and subcutaneous tissue disorders
Alopecia	16/115 (13.9%)		2/36 (5.6%)		8/104 (7.7%)		3/43 (7%)
Dry skin	15/115 (13%)		2/36 (5.6%)		3/104 (2.9%)		2/43 (4.7%)
Hypertrichosis	2/115 (1.7%)		2/36 (5.6%)		0/104 (0%)		0/43 (0%)
Onychoclasis	25/115 (21.7%)		11/36 (30.6%)		1/104 (1%)		0/43 (0%)
Pruritus	16/115 (13.9%)		2/36 (5.6%)		6/104 (5.8%)		4/43 (9.3%)
Rash	7/115 (6.1%)		0/36 (0%)		4/104 (3.8%)		2/43 (4.7%)
Skin lesion	1/115 (0.9%)		2/36 (5.6%)		3/104 (2.9%)		1/43 (2.3%)
Vascular disorders
Hot flush	13/115 (11.3%)		5/36 (13.9%)		25/104 (24%)		7/43 (16.3%)
Hypertension	14/115 (12.2%)		3/36 (8.3%)		4/104 (3.8%)		3/43 (7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.