Trial Outcomes & Findings for Dose-Escalation, Safety, Pharmacokinetics Study of Cabazitaxel With Gemcitabine In Patients With Solid Tumor (NCT NCT01001221)

NCT ID: NCT01001221

Last Updated: 2013-09-11

Results Overview

Dose Limiting Toxicities (DLTs) were defined as clinical adverse events (AE) or laboratory abnormalities considered drug-related as assessed by the Investigator or Sponsor, and achieving a Common Terminology Criteria for Adverse Events v3.0 (CTCAE) severity rating of severe (3) or life-threatening (4).

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 19 participants
• Primary outcome timeframe: Day 1 to Day 21 of the first treatment cycle
• Results posted on: 2013-09-11

Participant Flow

Participants were enrolled in 4 sites in the United States. Since it was not possible to determine the maximum Tolerated Dose (MTD) in study part 1, no participant was enrolled in study part 2 and the study was stopped.

At each dose level, there was a 1-week gap between the treatment of the first participant and the next 2 participants to evaluate toxicity. Before escalating to the next dose level, at least 3 participants were to be evaluable for the criteria defining dose limiting toxicity (DLT).

Participant milestones

Measure	Part 1: Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Part 1: Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Part 1: Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Part 1: Gemcitabine + Cabazitaxel Dose Level 0 gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Part 2: Cabazitaxel + Gemcitabine MTD Cabazitaxel IV and gemcitabine IV on Day 1 then, gemcitabine IV on Day 8 at the Maximum Tolerated Dose (MTD) as determined in study part 1 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Overall Study STARTED	5	5	3	6	0
Overall Study Treated	5	5	2	6	0
Overall Study Completed 1st Treatment Cycle	5	5	2	6	0
Overall Study COMPLETED	0	0	0	0	0
Overall Study NOT COMPLETED	5	5	3	6	0

Reasons for withdrawal

Measure	Part 1: Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Part 1: Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Part 1: Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Part 1: Gemcitabine + Cabazitaxel Dose Level 0 gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Part 2: Cabazitaxel + Gemcitabine MTD Cabazitaxel IV and gemcitabine IV on Day 1 then, gemcitabine IV on Day 8 at the Maximum Tolerated Dose (MTD) as determined in study part 1 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Overall Study Adverse Event	1	2	0	2	0
Overall Study Disease progression	3	2	2	4	0
Overall Study Other	1	1	0	0	0
Overall Study Not treated; protocol exclusion	0	0	1	0	0

Baseline Characteristics

Dose-Escalation, Safety, Pharmacokinetics Study of Cabazitaxel With Gemcitabine In Patients With Solid Tumor

Baseline characteristics by cohort

Measure	Part 1: Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Part 1: Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Part 1: Cabazitaxel + Gemcitabine Dose Level -2 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Part 1: Gemcitabine + Cabazitaxel Dose Level 0 n=6 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Total n=19 Participants Total of all reporting groups
Age Continuous	60.8 years STANDARD_DEVIATION 6.6 • n=5 Participants	59.2 years STANDARD_DEVIATION 9.2 • n=7 Participants	53.0 years STANDARD_DEVIATION 14.8 • n=5 Participants	56.3 years STANDARD_DEVIATION 16.1 • n=4 Participants	57.7 years STANDARD_DEVIATION 11.5 • n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	8 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	11 Participants n=21 Participants
Race/Ethnicity, Customized Asian/Oriental	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized Black	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized Caucasian/White	4 participants n=5 Participants	4 participants n=7 Participants	2 participants n=5 Participants	6 participants n=4 Participants	16 participants n=21 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Body Surface Area	1.87 m^2 STANDARD_DEVIATION 0.32 • n=5 Participants	1.82 m^2 STANDARD_DEVIATION 0.21 • n=7 Participants	1.98 m^2 STANDARD_DEVIATION 0.42 • n=5 Participants	1.84 m^2 STANDARD_DEVIATION 0.12 • n=4 Participants	1.87 m^2 STANDARD_DEVIATION 0.24 • n=21 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	0 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants	4 participants n=21 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	5 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	5 participants n=4 Participants	15 participants n=21 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants
Primary Tumor Site Bladder	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants	2 participants n=21 Participants
Primary Tumor Site Colon	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Primary Tumor Site Head/neck	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants
Primary Tumor Site Lung	2 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	4 participants n=21 Participants
Primary Tumor Site Muscle/soft tissue	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Primary Tumor Site Other	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Primary Tumor Site Ovaries	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Primary Tumor Site Pancreas	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	3 participants n=21 Participants
Primary Tumor Site Pelvis	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Primary Tumor Site Prostate	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants
Primary Tumor Site Skin	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Histological Type Adenocarcinoma	2 participants n=5 Participants	4 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	8 participants n=21 Participants
Histological Type Squamous cell carcinoma	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Histological Type Other	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants	4 participants n=4 Participants	10 participants n=21 Participants
Stage at Diagnosis Stage I	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants
Stage at Diagnosis Stage II	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Stage at Diagnosis Stage III	0 participants n=5 Participants	3 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	4 participants n=21 Participants
Stage at Diagnosis Stage IV	5 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	7 participants n=21 Participants
Stage at Diagnosis Unknown	0 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants	7 participants n=21 Participants
Number of Organs Involved	4.0 organs STANDARD_DEVIATION 1.6 • n=5 Participants	2.6 organs STANDARD_DEVIATION 0.5 • n=7 Participants	3.3 organs STANDARD_DEVIATION 0.6 • n=5 Participants	2.0 organs STANDARD_DEVIATION 0.6 • n=4 Participants	2.9 organs STANDARD_DEVIATION 1.2 • n=21 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 21 of the first treatment cycle

Population: DLT population: All participants who completed assessments for DLT evaluation for Cycle 1 and either: * received study treatment during Cycle 1 and had DLT or * did not have DLT and received a full dose of study treatment (no delay/reduction) during Cycle 1 and did not receive hematopoietic growth factors.

Dose Limiting Toxicities (DLTs) were defined as clinical adverse events (AE) or laboratory abnormalities considered drug-related as assessed by the Investigator or Sponsor, and achieving a Common Terminology Criteria for Adverse Events v3.0 (CTCAE) severity rating of severe (3) or life-threatening (4).

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Participants With Dose Limiting Toxicities During Dose Escalation	2 participants	2 participants	2 participants	2 participants

PRIMARY outcome

Timeframe: Fron Day 1 up to a maximum of 12 months

Objective response was defined as a confirmed complete response (CR) or a confirmed partial response (PR) during the treatment period, based on RECIST 1.1, as assessed by the Investigator.

CR: Disappearance of all target lesions, all non-target lesions, and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm.

PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion.

The objective response rate (ORR) was to be calculated as the proportion of participants with confirmed objective response relative to the total number of participants in the analysis population. Due to the inability to determine MTD during the study part 1, the analysis was not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Fron Day 1 up to a maximum of 12 months

Time to progression (TTP) was defined as the time from first treatment administration to first documentation of RECIST-defined objective tumor progression (>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of >=1 new lesion and/or unequivocal progression of existing non-target lesions).

Median TTP was to be estimated using the Kaplan-Meier method. Due to the inability to determine MTD during the study part 1, the analysis was not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Fron Day 1 up to a maximum of 12 months

Duration of Response (DR) was defined as the time from the first documentation of RECIST-defined objective tumor response to the first documentation of RECIST-defined objective tumor progression or death.

Median DR was to be estimated using the Kaplan-Meier method. Due to the inability to determine MTD during the study part 1, the analysis was not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)

Population: all treated (AT) population: All enrolled participants who received at least 1 part of a dose of study treatment

Summary of participants with adverse events (AEs) according to severity and relationship to study drug as assessed by the investigator. The National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), version 3.0 was used to grade the severity of AE.

Treatment-emergent adverse events (TEAEs) are AEs that occurred or worsened from start of treatment up to 30 days after treatment ceased.

NCI CTCAE v.3.0 grade 3 =severe and grade 4= life-threatening or disabling.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=6 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Participants With Adverse Events - Drug-related TEAE	6 participants	5 participants	2 participants	5 participants
Participants With Adverse Events AE leading to dose delay	4 participants	4 participants	1 participants	2 participants
Participants With Adverse Events Any AE	6 participants	5 participants	2 participants	5 participants
Participants With Adverse Events Any TEAE	6 participants	5 participants	2 participants	5 participants
Participants With Adverse Events Grade 3-4 TEAE	6 participants	5 participants	2 participants	5 participants
Participants With Adverse Events - Grade 3-4 drug-related TEAE	6 participants	4 participants	2 participants	5 participants
Participants With Adverse Events Serious TEAE	4 participants	5 participants	2 participants	2 participants
Participants With Adverse Events - Drug-related serious TEAE	3 participants	3 participants	2 participants	2 participants
Participants With Adverse Events AE leading to drug withdrawn	2 participants	2 participants	0 participants	2 participants
Participants With Adverse Events - Drug-related AE leading to drug withdrawn	1 participants	0 participants	0 participants	2 participants
Participants With Adverse Events AE leading to death	0 participants	1 participants	0 participants	0 participants
Participants With Adverse Events AE leading to dose reduction	4 participants	3 participants	2 participants	4 participants

SECONDARY outcome

Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion

Population: PK population: All enrolled participants who received at least 1 part of a dose of study treatment and had at least 1 post treatment analyzable PK sample, and with no prohibited concomitant medications

Blood samples for cabazitaxel assay were collected during cycle 1 and cabazitaxel plasma concentrations were determined using a validated liquid chromatography with tandem mass spectometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1 ng/mL.

Pharmacokinetic (PK) parameters were calculated from plasma concentrations using non-compartmental analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=6 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=4 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Cabazitaxel on Cycle 1: Maximum Plasma Concentration Observed (Cmax)	118 ng/ml Standard Deviation 43.9	123 ng/ml Standard Deviation 43.7	273 ng/ml Standard Deviation 21.9	150 ng/ml Standard Deviation 80.9

SECONDARY outcome

Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion

Population: PK population as previously defined

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=6 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=4 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Cabazitaxel on Cycle 1: Time to Maximum Concentration (Tmax)	0.93 hours (hr) Interval 0.92 to 1.03	1.00 hours (hr) Interval 0.92 to 1.05	0.94 hours (hr) Interval 0.88 to 1.0	0.94 hours (hr) Interval 0.87 to 0.95

SECONDARY outcome

Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion

Population: PK population as previously defined

Area under the plasma concentration versus time curve calculated using the trapezoidal method from time 0 to the last measurable concentration at time t.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=6 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=4 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Cabazitaxel on Cycle 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)	315 ng*hr/ml Standard Deviation 208	556 ng*hr/ml Standard Deviation 500	344 ng*hr/ml Standard Deviation 114	352 ng*hr/ml Standard Deviation 101

SECONDARY outcome

Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion

Population: PK population as previously defined. Six participants' assays could not be used for AUC.

Area under the plasma concentration versus time curve extrapolated to infinity

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=3 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Cabazitaxel on Cycle 1: Area Under the Time Concentration Curve (AUC)	306 ng*hr/ml Standard Deviation 50.1	876 ng*hr/ml Standard Deviation 730	462 ng*hr/ml Standard Deviation 156	420 ng*hr/ml Standard Deviation 77.3

SECONDARY outcome

Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion

Population: PK population as previously defined

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=6 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=4 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Cabazitaxel on Cycle 1: Terminal Half-life (t1/2z)	70.3 hours (hr) Standard Deviation 43.1	92.1 hours (hr) Standard Deviation 40.3	75.6 hours (hr) Standard Deviation 27.8	88.3 hours (hr) Standard Deviation 35.1

SECONDARY outcome

Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion

Population: PK population as previously defined. Six participants' assays could not be used for CL.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=3 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Cabazitaxel on Cycle 1: Total Plasma Clearance (CL)	90.8 L/hr Standard Deviation 7.15	61.0 L/hr Standard Deviation 38.4	59.5 L/hr Standard Deviation 6.38	64.3 L/hr Standard Deviation 16.2

SECONDARY outcome

Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion

Population: PK population as previously defined. One participant's assay could not be used for Vss.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=4 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Cabazitaxel on Cycle 1: Volume of Distribution at Steady State (Vss)	5570 L Standard Deviation 2100	6780 L Standard Deviation 3250	3930 L Standard Deviation 1170	4980 L Standard Deviation 818

SECONDARY outcome

Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion

Population: PK population as previously defined. Six participants' assays could not be used for CL/BSA.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=3 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Cabazitaxel on Cycle 1: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA)	49.6 L/hr/m^2 Standard Deviation 8.56	32.4 L/hr/m^2 Standard Deviation 18.3	31.9 L/hr/m^2 Standard Deviation 12.6	36.1 L/hr/m^2 Standard Deviation 6.58

SECONDARY outcome

Timeframe: before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion

Population: PK population as previously defined. One participant's assays could not be used for Vss/BSA.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=4 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Cabazitaxel on Cycle 1: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA)	3020 L/m^2 Standard Deviation 1130	3530 L/m^2 Standard Deviation 1650	1980 L/m^2 Standard Deviation 8.83	2690 L/m^2 Standard Deviation 434

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined.

Blood samples for gemcitabine assay were collected on Day 1 of cycle 1 at the following timepoints:

• Cabazitaxel + Gemcitabine: prior the start of cabazitaxel infusion, immediately before the end of gemcitabine infusion, 15, 30 minutes, 1.5, 3.5 and 22.5 hours after the end of gemcitabine infusion;
• Gemcitabine + cabazitaxel: prior the start of gemcitabine infusion, immediately before the end of gemcitabine infusion, 15, 30 minutes, 1, 1.5, 2.5, 9 and 23.5 hours after the end of cabazitaxel infusion;

Gemcitabine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL.

PK parameters were calculated from plasma concentrations using non-compartmental analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=4 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Maximum Plasma Concentration Observed (Cmax)	19000 ng/ml Standard Deviation 9130	14600 ng/ml Standard Deviation 6050	11400 ng/ml Standard Deviation 3270	35600 ng/ml Standard Deviation 27200

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=4 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Time to Maximum Concentration (Tmax)	0.42 hours (hr) Interval 0.37 to 0.5	0.49 hours (hr) Interval 0.47 to 0.5	0.60 hours (hr) Interval 0.53 to 0.67	0.38 hours (hr) Interval 0.37 to 0.55

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=4 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)	9920 ng*hr/ml Standard Deviation 5290	7320 ng*hr/ml Standard Deviation 1650	6120 ng*hr/ml Standard Deviation 3350	16000 ng*hr/ml Standard Deviation 11100

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined. Five participants' assays could not be used in the analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=1 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Area Under the Time Concentration Curve (AUC)	9970 ng*hr/ml Standard Deviation 5310	6290 ng*hr/ml Standard Deviation 1440	8530 ng*hr/ml Standard Deviation NA Single participant in analysis	21900 ng*hr/ml Standard Deviation 10800

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined. Five participants' assays could not be used in the analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=1 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Terminal Half-life (t1/2z)	0.256 hours Standard Deviation 0.0933	0.295 hours Standard Deviation 0.118	0.202 hours Standard Deviation NA Single participant in analysis	0.254 hours Standard Deviation 0.0570

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined. Five participants' assays could not be used in the analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=1 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Total Plasma Clearance (CL)	174 L/hr Standard Deviation 106	313 L/hr Standard Deviation 120	123 L/hr Standard Deviation NA Single participant in analysis	85.1 L/hr Standard Deviation 40.6

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined. Five participants' assays could not be used in the analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=1 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Volume of Distribution at Steady State (Vss)	51.6 L Standard Deviation 28.8	135 L Standard Deviation 86.2	47.0 L Standard Deviation NA Single participant in analysis	28.9 L Standard Deviation 30.4

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined. Five participants' assays could not be used in the analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=1 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA)	96.4 L/hr/m^2 Standard Deviation 62.8	159 L/hr/m^2 Standard Deviation 31.3	78.4 L/hr/m^2 Standard Deviation NA Single participant in analysis	49.8 L/hr/m^2 Standard Deviation 27.0

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined. Five participants' assays could not be used in the analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=1 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA)	28.7 L/m^2 Standard Deviation 17.4	66.5 L/m^2 Standard Deviation 31.7	29.9 L/m^2 Standard Deviation NA Single participant in analysis	17.3 L/m^2 Standard Deviation 18.9

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined

Blood samples for gemcitabine assay were collected on Day 8 of cycle 1 at the following timepoints:

• Cabazitaxel + Gemcitabine: prior the start of infusion, immediately before the end of infusion, 15, 30 minutes, 1.5, 3.5 and 22.5 hours after the end of infusion;
• Gemcitabine + cabazitaxel: prior the start of infusion, immediately before the end of infusion, 15, 30 minutes, 1, 1.5, 2.5, 9 and 23.5 hours after the end of infusion;

Gemcitabine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL.

PK parameters were calculated from plasma concentrations using non-compartmental analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=4 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Maximum Plasma Concentration Observed (Cmax)	14100 ng/ml Standard Deviation 12200	10200 ng/ml Standard Deviation 283	—	34500 ng/ml Standard Deviation 30800

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=4 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Time to Maximum Concentration (Tmax)	0.47 hours (hr) Interval 0.4 to 0.48	0.52 hours (hr) Interval 0.52 to 0.52	—	0.45 hours (hr) Interval 0.42 to 0.55

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=4 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)	7710 ng*hr/ml Standard Deviation 6840	5530 ng*hr/ml Standard Deviation 1150	—	15300 ng*hr/ml Standard Deviation 11900

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined. Two participants' assays could not be used in the analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=1 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Terminal Half-life (t1/2z)	0.317 hours (hr) Standard Deviation 0.113	0.222 hours (hr) Standard Deviation NA Single participant in analysis	—	0.282 hours (hr) Standard Deviation 0.0218

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined. Two participants' assays could not be used in the analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=1 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Area Under the Time Concentration Curve (AUC)	7780 ng*hr/ml Standard Deviation 6880	6360 ng*hr/ml Standard Deviation NA Single participant in analysis	—	18500 ng*hr/ml Standard Deviation 12300

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined. Two participants' assays could not be used in the analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=1 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Total Plasma Clearance (CL)	252 L/hr Standard Deviation 158	262 L/hr Standard Deviation NA Single participant in analysis	—	110 L/hr Standard Deviation 55.8

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined. Two participants' assays could not be used in the analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=1 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Volume of Distribution at Steady State (Vss)	93.3 L Standard Deviation 51.7	104 L Standard Deviation NA Single participant in analysis	—	36.2 L Standard Deviation 19.4

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined. Two participants' assays could not be used in the analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=1 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA)	143 L/hr/m^2 Standard Deviation 93.3	157 L/hr/m^2 Standard Deviation NA Single participant in analysis	—	62.8 L/hr/m^2 Standard Deviation 32.7

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined. Two participants' assays could not be used in the analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=1 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA)	52.3 L/m^2 Standard Deviation 28.6	62.2 L/m^2 Standard Deviation NA Single participant in analysis	—	20.6 L/m^2 Standard Deviation 11.6

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined

Blood samples collected for gemcitabine assay were used to assay gemcitabine metabolite, 2',2' difluorodeoxyuridine(dFdU).

2',2' difluorodeoxyuridine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL.

PK parameters were calculated from plasma concentrations using non-compartmental analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Maximum Plasma Concentration Observed (Cmax)	21100 ng/ml Standard Deviation 5980	32200 ng/ml Standard Deviation 10000	25500 ng/ml Standard Deviation 8770	32500 ng/ml Standard Deviation 10800

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Time to Maximum Concentration (Tmax)	0.77 hours Interval 0.5 to 1.47	0.73 hours Interval 0.5 to 0.77	0.65 hours Interval 0.53 to 0.77	0.77 hours Interval 0.47 to 0.83

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)	168000 ng*hr/ml Standard Deviation 57000	227000 ng*hr/ml Standard Deviation 27500	167000 ng*hr/ml Standard Deviation 47500	235000 ng*hr/ml Standard Deviation 47400

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=5 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Terminal Half-life (t1/2z)	12.1 hours Standard Deviation 5.17	9.07 hours Standard Deviation 2.22	7.96 hours Standard Deviation 1.87	9.41 hours Standard Deviation 0.837

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined. Two participants' assays could not be used in the analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Area Under the Time Concentration Curve (AUC)	151000 ng*hr/ml Standard Deviation 37700	273000 ng*hr/ml Standard Deviation 58100	191000 ng*hr/ml Standard Deviation 66900	285000 ng*hr/ml Standard Deviation 61200

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: All enrolled participants who received at least 1 part of a dose of study treatment and had at least 1 post treatment analyzable PK sample and with no prohibited concomitant medications.

Blood samples collected for gemcitabine assay were used to assay gemcitabine metabolite, 2',2' difluorodeoxyuridine(dFdU).

2',2' difluorodeoxyuridine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL.

PK parameters were calculated from plasma concentrations using non-compartmental analysis.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Maximum Plasma Concentration Observed (Cmax)	18700 ng/ml Standard Deviation 4740	27400 ng/ml Standard Deviation 3180	—	34800 ng/ml Standard Deviation 8630

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Time to Maximum Concentration (Tmax)	0.72 hours Interval 0.7 to 1.0	0.69 hours Interval 0.52 to 0.85	—	0.68 hours Interval 0.55 to 1.02

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)	141000 ng*hr/ml Standard Deviation 26400	216000 ng*hr/ml Standard Deviation 3700	—	287000 ng*hr/ml Standard Deviation 77500

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Terminal Half-life (t1/2z)	9.10 hours Standard Deviation 0.484	7.29 hours Standard Deviation 1.11	—	8.55 hours Standard Deviation 0.820

SECONDARY outcome

Timeframe: 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1

Population: PK population as previously defined

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=2 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Area Under the Time Concentration Curve (AUC)	168000 ng*hr/ml Standard Deviation 27600	240000 ng*hr/ml Standard Deviation 11300	—	340000 ng*hr/ml Standard Deviation 100000

SECONDARY outcome

Timeframe: Day 1 (7 to 9 timepoints from start of infusion up to 24h hours after the end of infusion) and Day 8 (7 to 9 timepoints from start of infusion up to 24h hours after the end of infusion)

Population: Enrolled participants who received at least 1 part of a dose of study treatment and had valid Day 1 and Day 8 PK samples. Valid PK samples included at least 1 post treatment analyzable PK sample and no prohibited concomitant medications.

Ratio Day 1/Day 8 for AUClast and AUC were calculated to assess the effect of cabazitaxel on gemcitabine exposure.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=3 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=1 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=3 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Pharmacokinetic of Gemcitabine on Cycle 1: Ratio Day 1/Day 8 for AUClast and AUC AUClast	1.11 ratio Interval 0.994 to 1.25	1.15 ratio Single participant in analysis	—	1.17 ratio Interval 0.661 to 2.49
Pharmacokinetic of Gemcitabine on Cycle 1: Ratio Day 1/Day 8 for AUClast and AUC AUC	1.11 ratio Interval 0.994 to 1.25	1.15 ratio Single participant in analysis	—	1.24 ratio Interval 0.66 to 2.47

POST_HOC outcome

Timeframe: Up to a maximum of 22 cycles (median 4 cycles)

Population: all treated (AT) population: All enrolled participants who received at least 1 part of a dose of study treatment.

Participant Best response was assessed by investigator using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1:

• Complete response (CR): Disappearance of all target lesions, all non-target lesions, and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm:
• Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion;
• Progressive disease (PD): >=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of >=1 new lesion and/or unequivocal progression of existing non-target lesions;
• Stable disease (SD): not a CR, PR or PD.

Outcome measures

Measure	Gemcitabine + Cabazitaxel Dose Level 0 n=6 Participants Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level 0 n=5 Participants Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 Participants Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Participant Best Response as Per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Complete response	0 participants	0 participants	0 participants	0 participants
Participant Best Response as Per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Partial response	1 participants	1 participants	0 participants	1 participants
Participant Best Response as Per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Stable disease	3 participants	2 participants	0 participants	3 participants
Participant Best Response as Per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Progressive disease	2 participants	1 participants	2 participants	1 participants
Participant Best Response as Per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Not evaluable	0 participants	1 participants	0 participants	0 participants

Adverse Events

Cabazitaxel + Gemcitabine Dose Level 0

Serious events: 5 serious events

Other events: 5 other events

Deaths: 0 deaths

Cabazitaxel + Gemcitabine Dose Level -1

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Cabazitaxel + Gemcitabine Dose Level -2

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Gemcitabine + Cabazitaxel Dose Level 0

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cabazitaxel + Gemcitabine Dose Level 0 n=5 participants at risk Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 participants at risk Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 participants at risk Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Gemcitabine + Cabazitaxel Dose Level 0 n=6 participants at risk Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Infections and infestations Bronchiolitis	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Infections and infestations Pneumonia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Infections and infestations Sepsis	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Blood and lymphatic system disorders Febrile neutropenia	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	100.0% 2/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Blood and lymphatic system disorders Neutropenia	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Blood and lymphatic system disorders Pancytopenia	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Blood and lymphatic system disorders Leukopenia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Nervous system disorders Headache	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Cardiac disorders Supraventricular tachycardia	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Hypoxia	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Gastrointestinal disorders Intestinal dilatation	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Gastrointestinal disorders Intestinal obstruction	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Disease progression	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Chest pain	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Pyrexia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Investigations Blood electrolytes abnormal	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Investigations Aspartate aminotransferase increased	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)

Other adverse events

Measure	Cabazitaxel + Gemcitabine Dose Level 0 n=5 participants at risk Cabazitaxel 20 mg/m\^2 IV followed by gemcitabine 1000 mg/m\^2 IV on Day 1 then, gemcitabine 1000 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -1 n=5 participants at risk Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 900 mg/m\^2 IV on Day 1 then, gemcitabine 900 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Cabazitaxel + Gemcitabine Dose Level -2 n=2 participants at risk Cabazitaxel 15 mg/m\^2 IV followed by gemcitabine 700 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision	Gemcitabine + Cabazitaxel Dose Level 0 n=6 participants at risk Gemcitabine 700 mg/m\^2 IV followed by cabazitaxel 15 mg/m\^2 IV on Day 1 then, gemcitabine 700 mg/m\^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision
Gastrointestinal disorders Oral pain	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Gastrointestinal disorders Vomiting	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	40.0% 2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Skin and subcutaneous tissue disorders Rash	40.0% 2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Skin and subcutaneous tissue disorders Hyperkeratosis	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Musculoskeletal and connective tissue disorders Back pain	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Musculoskeletal and connective tissue disorders Arthalgia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	33.3% 2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Infections and infestations Upper respiratory tract infection	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Infections and infestations Eye infection	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Infections and infestations Gastroenteritis viral	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Infections and infestations Oral herpes	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Infections and infestations Urinary tract infection	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Infections and infestations Viral infection	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Infections and infestations Viral upper respiratory tract infection	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Blood and lymphatic system disorders Neutropenia	80.0% 4/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	60.0% 3/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 3/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Blood and lymphatic system disorders Lymphopenia	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Blood and lymphatic system disorders Thrombocytopenia	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	40.0% 2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 3/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Blood and lymphatic system disorders Anaemia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	66.7% 4/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Blood and lymphatic system disorders Leukopenia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Blood and lymphatic system disorders Normochromic normocytic anaemia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Immune system disorders Drug hypersensitivity	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Metabolism and nutrition disorders Decreased appetite	40.0% 2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	60.0% 3/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	66.7% 4/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Metabolism and nutrition disorders Dehydration	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Metabolism and nutrition disorders Hypokalaemia	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Metabolism and nutrition disorders Hypophosphataemia	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Metabolism and nutrition disorders Gout	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Psychiatric disorders Abnormal dreams	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Psychiatric disorders Depression	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Psychiatric disorders Insomnia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	33.3% 2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Nervous system disorders Neuropathy peripheral	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Nervous system disorders Paraesthesia	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Nervous system disorders Balance disorder	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Nervous system disorders Dizziness	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	40.0% 2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Nervous system disorders Dysgeusia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	33.3% 2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Nervous system disorders Headache	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Nervous system disorders Memory impairment	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Nervous system disorders Somnolence	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Eye disorders Vision blurred	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Eye disorders Vitreous floaters	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	40.0% 2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Vascular disorders Hypotension	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Vascular disorders Orthostatic hypotension	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Cough	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	33.3% 2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Dyspnoea	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Hypoxia	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Nasal congestion	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Productive cough	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	100.0% 2/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Gastrointestinal disorders Diarrhoea	40.0% 2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	80.0% 4/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	33.3% 2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Gastrointestinal disorders Abdominal pain	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Gastrointestinal disorders Abdominal pain upper	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Gastrointestinal disorders Constipation	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Gastrointestinal disorders Nausea	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	80.0% 4/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	33.3% 2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Gastrointestinal disorders Abdominal distension	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Gastrointestinal disorders Dry mouth	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Gastrointestinal disorders Dyspepsia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Gastrointestinal disorders Flatulence	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Reproductive system and breast disorders Vaginal discharge	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Asthenia	40.0% 2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	40.0% 2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Fatigue	40.0% 2/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	80.0% 4/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	83.3% 5/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Chest discomfort	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Chills	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Pain	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Catheter site haematoma	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Catheter site pain	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Early satiety	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Generalized oedema	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Injection site reaction	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Musosal inflammation	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Oedema peripheral	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 3/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
General disorders Pyrexia	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	33.3% 2/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Investigations Weight decreased	60.0% 3/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	50.0% 1/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Investigations Alanine aminotransferase increased	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Investigations Aspartate aminotransferase increased	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Investigations Blood alkalne phosphatase increased	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	16.7% 1/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Injury, poisoning and procedural complications Excoriation	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Injury, poisoning and procedural complications Anastomotic ulcer	0.00% 0/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	20.0% 1/5 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/2 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)	0.00% 0/6 • from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)

Additional Information

Trial Transparency Team

sanofi-aventis

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Results disclosure agreements

• Principal investigator is a sponsor employee At least 45 days in advance of proposed submission, the Investigator should forward a copy of the manuscript or abstract for review by the sponsor, and, if necessary, delay publication or communication for a limited time in order to protect the confidentiality or proprietary nature of any information contained therein.
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