Trial Outcomes & Findings for E7080 in Combination With Carboplatin + Gemcitabine Versus Carboplatin + Gemcitabine Alone as Second Line Therapy in Patients With Platinum-Sensitive Recurrent Ovarian Cancer by CA125 (NCT NCT01133756)

Last Updated: 2023-06-22

Results Overview

DLTs were defined as clinically significant adverse events occurring less than or equal to 21 days after commencing study treatment and considered to be possibly or probably related to study treatment by the Investigator. If 1 DLT occurred at any dose level, the cohort was to be expanded to include a maximum of six evaluable subjects. If 2 DLTs occurred at any dose level, the maximum tolerated dose (MTD) was to be either defined as the preceding dose, or an intermediate dose. To evaluate an intermediate dose, an additional dose cohort could be added to more accurately define the MTD.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

7 participants

Primary outcome timeframe

Cycle 1 (21 days)

Results posted on

2023-06-22

Participant Flow

Approximately, 100 participants were planned to be enrolled (10-20 in Phase 1b and 80 in Phase 2) but only 7 participants were enrolled.

Participant milestones

Participant milestones
Measure	Lenvatinib 16 mg (Day 1 to Day 21) + Carboplatin + Gemcitabine Participants received carboplatin (area under the concentration-time curve \[AUC\] 4) + gemcitabine (1000 mg/m2) intravenous (IV) infusion over 30 minutes in combination with lenvatinib 16 mg on Day 1 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.	Lenvatinib 16 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine Participants received carboplatin (AUC 4) + gemcitabine (1000 mg/m2) IV infusion over 30 minutes in combination with lenvatinib 16 mg on Day 2 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.	Lenvatinib 8 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine Participants received carboplatin (AUC 4) + gemcitabine (1000 mg/m2) IV infusion over 30 minutes in combination with lenvatinib 8 mg on Day 2 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.
Overall Study STARTED	2	3	2
Overall Study Completed 6 Cycles	1	0	0
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	2	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Lenvatinib 16 mg (Day 1 to Day 21) + Carboplatin + Gemcitabine Participants received carboplatin (area under the concentration-time curve \[AUC\] 4) + gemcitabine (1000 mg/m2) intravenous (IV) infusion over 30 minutes in combination with lenvatinib 16 mg on Day 1 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.	Lenvatinib 16 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine Participants received carboplatin (AUC 4) + gemcitabine (1000 mg/m2) IV infusion over 30 minutes in combination with lenvatinib 16 mg on Day 2 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.	Lenvatinib 8 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine Participants received carboplatin (AUC 4) + gemcitabine (1000 mg/m2) IV infusion over 30 minutes in combination with lenvatinib 8 mg on Day 2 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.
Overall Study Adverse Event	1	2	1
Overall Study Investigator Decision	1	0	0
Overall Study Withdrawal by Subject	0	1	0
Overall Study Progression of Disease	0	0	1

Baseline Characteristics

E7080 in Combination With Carboplatin + Gemcitabine Versus Carboplatin + Gemcitabine Alone as Second Line Therapy in Patients With Platinum-Sensitive Recurrent Ovarian Cancer by CA125

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lenvatinib 16 mg (Day 1 to Day 21) + Carboplatin + Gemcitabine n=2 Participants Participants received carboplatin (AUC 4) + gemcitabine (1000 mg/m2) IV infusion over 30 minutes in combination with lenvatinib 16 mg on Day 1 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.	Lenvatinib 16 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine n=3 Participants Participants received carboplatin (AUC 4) + gemcitabine (1000 mg/m2) IV infusion over 30 minutes in combination with lenvatinib 16 mg on Day 2 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.	Lenvatinib 8 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine n=2 Participants Participants received carboplatin (AUC 4) + gemcitabine (1000 mg/m2) IV infusion over 30 minutes in combination with lenvatinib 8 mg on Day 2 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.	Total n=7 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Cycle 1 (21 days)

Population: Safety analysis was evaluated based on Safety Population, defined as all subjects enrolled into the Phase 1b portion of this study, except for those who (i) dropped out of the study prior to receiving any study drug, or (ii) were without any safety assessments following the first dose of study drug.

Outcome measures

Outcome measures
Measure	Lenvatinib 16 mg (Day 1 to Day 21) + Carboplatin + Gemcitabine n=2 Participants Participants received carboplatin (AUC 4) + gemcitabine (1000 mg/m2) IV infusion over 30 minutes in combination with lenvatinib 16 mg on Day 1 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.	Lenvatinib 16 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine n=3 Participants Participants received carboplatin (AUC 4) + gemcitabine (1000 mg/m2) IV infusion over 30 minutes in combination with lenvatinib 16 mg on Day 2 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.	Lenvatinib 8 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine n=2 Participants Participants received carboplatin (AUC 4) + gemcitabine (1000 mg/m2) IV infusion over 30 minutes in combination with lenvatinib 8 mg on Day 2 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.
Number of Participants With Dose Limiting Toxicity (DLT) Platelet count decreased	1 Participants	0 Participants	0 Participants
Number of Participants With Dose Limiting Toxicity (DLT) Thrombocytopenia	0 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 of every cycle, at end of treatment visit and every 2 months during follow-up period for patients who complete study without progressive disease.

Population: Due to the limited enrollment despite significant diligence to boost enrollment and the complex study design required to manage hematologic toxicity, the study was terminated before the initiation of Phase 2. Hence the analysis was not conducted.

Due to the limited enrollment despite significant diligence to boost enrollment and the complex study design required to manage hematologic toxicity, the study was terminated before the initiation of Phase 2. Hence the analysis was not conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 12

Outcome measures

Outcome data not reported

Adverse Events

Lenvatinib 16 mg (Day 1 to Day 21) + Carboplatin + Gemcitabine

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Lenvatinib 16 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Lenvatinib 8 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Eisai Medical Services

Eisai Inc.

Phone: 1-888-422-4743

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Lenvatinib 16 mg (Day 1 to Day 21) + Carboplatin + Gemcitabine n=2 participants at risk Participants received carboplatin (AUC 4) + gemcitabine (1000 mg/m2) IV infusion over 30 minutes in combination with lenvatinib 16 mg on Day 1 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.	Lenvatinib 16 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine n=3 participants at risk Participants received carboplatin (AUC 4) + gemcitabine (1000 mg/m2) IV infusion over 30 minutes in combination with lenvatinib 16 mg on Day 2 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.	Lenvatinib 8 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine n=2 participants at risk Participants received carboplatin (AUC 4) + gemcitabine (1000 mg/m2) intravenous (IV) infusion over 30 minutes in combination with lenvatinib 8 mg on Day 2 of 21-day cycle and gemcitabine (1000 mg/m2) alone on Day 8 of the cycle.
Blood and lymphatic system disorders ANAEMIA	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	66.7% 2/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Blood and lymphatic system disorders NEUTROPENIA	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	66.7% 2/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Blood and lymphatic system disorders THROMBOCYTOPENIA	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	66.7% 2/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Cardiac disorders BRADYCARDIA	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	33.3% 1/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Gastrointestinal disorders ABDOMINAL DISCOMFORT	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Gastrointestinal disorders ABDOMINAL DISTENSION	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Gastrointestinal disorders CONSTIPATION	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	33.3% 1/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Gastrointestinal disorders DIARRHOEA	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Gastrointestinal disorders DRY MOUTH	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Gastrointestinal disorders FLATULENCE	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Gastrointestinal disorders LIP SWELLING	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	33.3% 1/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Gastrointestinal disorders NAUSEA	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	33.3% 1/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Gastrointestinal disorders ORAL DISORDER	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	33.3% 1/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Gastrointestinal disorders STOMATITIS	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Gastrointestinal disorders VOMITING	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
General disorders CHEST PAIN	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
General disorders FATIGUE	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	66.7% 2/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
General disorders OEDEMA PERIPHERAL	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Hepatobiliary disorders HYPERBILIRUBINAEMIA	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Immune system disorders SEASONAL ALLERGY	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Infections and infestations ABSCESS NECK	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Infections and infestations GASTROENTERITIS VIRAL	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	33.3% 1/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Infections and infestations LOCALISED INFECTION	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Infections and infestations NASOPHARYNGITIS	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Infections and infestations URINARY TRACT INFECTION	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Injury, poisoning and procedural complications INCISIONAL HERNIA	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Investigations BLOOD ALBUMIN DECREASED	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Investigations BLOOD MAGNESIUM DECREASED	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Investigations BLOOD PRESSURE INCREASED	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Investigations HAEMATOCRIT DECREASED	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Investigations LYMPHOCYTE COUNT DECREASED	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	33.3% 1/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Investigations WHITE BLOOD CELL COUNT DECREASED	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	33.3% 1/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Metabolism and nutrition disorders DECREASED APPETITE	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Metabolism and nutrition disorders HYPOKALAEMIA	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Metabolism and nutrition disorders HYPOMAGNESAEMIA	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Musculoskeletal and connective tissue disorders ARTHRALGIA	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Nervous system disorders DYSGEUSIA	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.
Nervous system disorders HEADACHE	50.0% 1/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/3 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.	0.00% 0/2 • For each participant, from the first dose till 30 days after the last dose or up to 18 Sep 2012 or up to 2.5 years Treatment emergent adverse events (defined as an adverse event (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) are reported.