Neoplasms
Conditions
Keywords
Advanced cancer
Brief summary
To determine the overall safety of PF-00477736 when given in combination with gemcitabine, a chemotherapy agent, in patients with advanced solid tumors and determine the maximum dose of PF-00477736 that can be safely given in combination with gemcitabine. This is the first study of PF-00477736 in humans.
Detailed description
The study was closed to enrollment as of 17 May 2010 due to business reasons. The patient on study continued treatment until 19 April 2011 when stopped for complete response. Premature closure was not prompted by any safety or efficacy concerns.
Interventions
DRUGPF-00477736
* Escalating doses of PF-00477736 will be administered intravenously on Days 2 and 9 and gemcitabine will be administered intravenously on Days 1 and 8 of a 21-day cycle (doses to be evaluated range from 750 to 1250 mg/m2 in three separated cohorts). * If a patient is administered Cycle 0 - only PF-0047736 will be administered intravenously on Days 1 and 8 of a 21-day cycle for patients who have a 3-hour infusion and Days 1 and 8 of a 14-day cycle for patients who have a 24-hour infusion.
DRUGgemcitabine
gemcitabine will be administered intravenously on Days 1 and 8 of a 21-day cycle (doses to be evaluated range from 750 to 1250 mg/m2 in three separated cohorts).
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological or cytopathological diagnosis of solid malignancy that is refractory to standard therapy or for which no curative therapy exists. * ECOG performance status 0 or 1. * Adequate blood cell counts, kidney function and liver function.
Exclusion criteria
* Prior treatment with gemcitabine. * Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. * NCI CTC Grade 2 or higher ARDS, non-infectious pneumonitis, or pulmonary fibrosis. * NCI CTC Grade 2 or higher cardiovascular toxicities with the exception of NCI CTC Grade 3 hypertension that is well controlled. * Known human immunodeficiency virus (HIV) seropositivity. * Concurrent treatment with anticoagulants or known coagulopathy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Dose (MTD) of PF-00477736 When Administered in Combination With Gemcitabine | Up to Day 21 Cycle 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 | — |
| Minimum Observed Plasma Trough Concentration (Cmin) | 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] | 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start: Day 1, 8 Cycle 0 | AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24). |
| Number of Participants With Objective Response (OR) | Baseline, Day 15 of Cycle 2 and 4 and every 4 cycles thereafter up to Week 62 | OR based assessment of confirmed complete response(CR)/confirmed partial response(PR)/stable disease(SD)/progressive disease(PD) as per Response Evaluation Criteria in Solid Tumors(RECIST).CR:disappearance of target lesions;PR:at least(\>=) 30% decrease in sum of longest dimensions of target lesions(reference:baseline sum of longest dimensions);PD:\>=20% increase in sum of longest dimensions of target lesions(reference:smallest sum of longest dimensions recorded since treatment started)/appearance of any new lesions;SD:no adequate shrinkage to qualify for PR/adequate increase to qualify for PD. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). |
| Concentration of PF-00477736 in Urine | 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 | — |
| Plasma Decay Half-Life (t1/2) | 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Metabolite Profile of PF-00477736 in Plasma and Urine | 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-48)] | 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 | AUC (0-48)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-48). |
Countries
Australia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-00477736 50 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 1) PF-00477736 50 mg 3 hrs infusion IV on Days 1 and 8 of cycle 0 and subsequently on Days 2 and 9 of each cycle (21 days cycle) for first 3 participants and on Days 2 and 9 of each cycle (21 days cycle), starting with cycle 1, for participants subsequently enrolled in this cohort. Gemcitabine 750 mg mg/m\^2 30 minutes infusion IV on Days 1 and 8 of each cycle (21 days cycle), starting with cycle 1. | 6 |
| PF-00477736 65 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 2) PF-00477736 65 mg 3 hrs infusion IV on Days 1 and 8 of cycle 0 and subsequently on Days 2 and 9 of each cycle (21 days cycle) for first 3 participants and on Days 2 and 9 of each cycle (21 days cycle), starting with cycle 1, for participants subsequently enrolled in this cohort. Gemcitabine 750 mg/m\^2 30 minutes infusion IV on Days 1 and 8 of each cycle (21 days cycle), starting with cycle 1. | 8 |
| PF-00477736 80 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 3) PF-00477736 80 mg 3 hrs infusion IV on Days 1 and 8 of cycle 0 and subsequently on Days 2 and 9 of each cycle (21 days cycle). Gemcitabine 750 mg/m\^2 30 minutes infusion IV on Days 1 and 8 of each cycle (21 days cycle), starting with cycle 1. | 3 |
| PF-00477736 80 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 4) PF-00477736 80 mg 24 hrs infusion IV on Days 1 and 8 of cycle 0 (14 days cycle) and subsequently on Days 2 and 9 of each cycle (21 days cycle). Gemcitabine 750 mg/m\^2 30 minutes infusion IV on Days 1 and 8 of each cycle (21 days cycle), starting with cycle 1. | 3 |
| PF-00477736 120 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 5) PF-00477736 120 mg 24 hrs infusion IV on Days 1 and 8 of cycle 0 (14 days cycle) and subsequently on Days 2 and 9 of each cycle (21 days cycle). Gemcitabine 750 mg/m\^2 30 minutes infusion IV on Days 1 and 8 of each cycle (21 days cycle), starting with cycle 1. | 3 |
| PF-00477736 180 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 6) PF-00477736 180 mg 24 hrs infusion IV on Days 1 and 8 of cycle 0 (14 days cycle) and subsequently on Days 2 and 9 of each cycle (21 days cycle). Gemcitabine 750 mg/m\^2 30 minutes infusion IV on Days 1 and 8 of each cycle (21 days cycle), starting with cycle 1. | 3 |
| PF-00477736 270 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 7) PF-00477736 270 mg 24 hrs infusion IV on Days 1 and 8 of cycle 0 (14 days cycle) and subsequently on Days 2 and 9 of each cycle (21 days cycle) for first 3 participants and on Days 2 and 9 of each cycle (21 days cycle), starting with cycle 1, for participants subsequently enrolled in this cohort. Gemcitabine 750 mg/m\^2 30 minutes infusion IV on Days 1 and 8 of each cycle (21 days cycle), starting with cycle 1. | 7 |
| PF-00477736 340 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 8) PF-00477736 340 mg 24 hrs infusion IV on Days 1 and 8 of cycle 0 (14 days cycle) and subsequently on Days 2 and 9 of each cycle (21 days cycle). Gemcitabine 750 mg/m\^2 30 minutes infusion IV on Days 1 and 8 of each cycle (21 days cycle), starting with cycle 1. | 3 |
| PF-00477736 180 mg 24 Hrs + Gemcitabine 1000 mg/m^2 (Cohort 9) PF-00477736 infusion 180 mg 24 hrs infusion IV on Days 2 and 9 of each cycle (21 days cycle). Gemcitabine infusion 1000 mg/m\^2 30 minutes infusion IV on Days 1 and 8 of each cycle (21 days cycle). | 3 |
| PF-00477736 225 mg 24 Hrs + Gemcitabine 1000 mg/m^2 (cohort10) PF-00477736 infusion 225 mg 24 hrs infusion IV on Days 2 and 9 of each cycle (21 days cycle). Gemcitabine infusion 1000 mg/m\^2 30 minutes infusion IV on Days 1 and 8 of each cycle (21 days cycle). | 4 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Objective progression or relapse | 5 | 6 | 2 | 3 | 3 | 3 | 6 | 1 | 2 | 2 |
| Overall Study | Other | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Study terminated by sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | PF-00477736 50 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 1) | PF-00477736 65 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 2) | PF-00477736 80 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 3) | PF-00477736 80 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 4) | PF-00477736 120 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 5) | PF-00477736 180 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 6) | PF-00477736 270 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 7) | PF-00477736 340 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 8) | PF-00477736 180 mg 24 Hrs + Gemcitabine 1000 mg/m^2 (Cohort 9) | PF-00477736 225 mg 24 Hrs + Gemcitabine 1000 mg/m^2 (cohort10) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | 55.2 years STANDARD_DEVIATION 18.3 | 62.3 years STANDARD_DEVIATION 6.8 | 55.0 years STANDARD_DEVIATION 5.2 | 45.0 years STANDARD_DEVIATION 3.6 | 55.0 years STANDARD_DEVIATION 11.5 | 44.3 years STANDARD_DEVIATION 12.1 | 54.0 years STANDARD_DEVIATION 8.9 | 55.7 years STANDARD_DEVIATION 4.6 | 46.0 years STANDARD_DEVIATION 6.9 | 49.5 years STANDARD_DEVIATION 7.1 | 53.7 years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 6 Participants | 2 Participants | 2 Participants | 2 Participants | 23 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 8 / 8 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 7 / 7 | 2 / 3 | 3 / 3 | 3 / 4 |
| serious Total, serious adverse events | 1 / 6 | 3 / 8 | 2 / 3 | 1 / 3 | 0 / 3 | 2 / 3 | 4 / 7 | 2 / 3 | 0 / 3 | 3 / 4 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of PF-00477736 When Administered in Combination With Gemcitabine
Time frame: Up to Day 21 Cycle 1
Population: Full analysis set (FAS) included all enrolled participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-00477736 + Gemcitabine 750 mg/m^2 | Maximum Tolerated Dose (MTD) of PF-00477736 When Administered in Combination With Gemcitabine | 270 mg |
| PF-00477736 + Gemcitabine 1000 mg/m^2 | Maximum Tolerated Dose (MTD) of PF-00477736 When Administered in Combination With Gemcitabine | NA mg |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)]
AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
Time frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start: Day 1, 8 Cycle 0
Population: Data was not analyzed, as study was terminated due to business reasons.
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-48)]
AUC (0-48)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-48).
Time frame: 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Population: Data was not analyzed, as study was terminated due to business reasons.
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Time frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Population: Data was not analyzed, as study was terminated due to business reasons.
Secondary
Concentration of PF-00477736 in Urine
Time frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Population: Data was not analyzed, as study was terminated due to business reasons.
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Population: Data was not analyzed, as study was terminated due to business reasons.
Secondary
Metabolite Profile of PF-00477736 in Plasma and Urine
Time frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Population: Data was not analyzed, as study was terminated due to business reasons.
Secondary
Minimum Observed Plasma Trough Concentration (Cmin)
Time frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Population: Data was not analyzed, as study was terminated due to business reasons.
Secondary
Number of Participants With Objective Response (OR)
OR based assessment of confirmed complete response(CR)/confirmed partial response(PR)/stable disease(SD)/progressive disease(PD) as per Response Evaluation Criteria in Solid Tumors(RECIST).CR:disappearance of target lesions;PR:at least(\>=) 30% decrease in sum of longest dimensions of target lesions(reference:baseline sum of longest dimensions);PD:\>=20% increase in sum of longest dimensions of target lesions(reference:smallest sum of longest dimensions recorded since treatment started)/appearance of any new lesions;SD:no adequate shrinkage to qualify for PR/adequate increase to qualify for PD.
Time frame: Baseline, Day 15 of Cycle 2 and 4 and every 4 cycles thereafter up to Week 62
Population: FAS included all enrolled participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-00477736 + Gemcitabine 750 mg/m^2 | Number of Participants With Objective Response (OR) | 1 participants |
| PF-00477736 + Gemcitabine 1000 mg/m^2 | Number of Participants With Objective Response (OR) | 0 participants |
| PF-00477736 80 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 3) | Number of Participants With Objective Response (OR) | 1 participants |
| PF-00477736 80 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 4) | Number of Participants With Objective Response (OR) | 1 participants |
| PF-00477736 120 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 5) | Number of Participants With Objective Response (OR) | 0 participants |
| PF-00477736 180 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 6) | Number of Participants With Objective Response (OR) | 0 participants |
| PF-00477736 270 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 7) | Number of Participants With Objective Response (OR) | 0 participants |
| PF-00477736 340 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 8) | Number of Participants With Objective Response (OR) | 0 participants |
| PF-00477736 180 mg 24 Hrs + Gemcitabine 1000 mg/m^2 (Cohort 9) | Number of Participants With Objective Response (OR) | 1 participants |
| PF-00477736 225 mg 24 Hrs + Gemcitabine 1000 mg/m^2 (cohort10) | Number of Participants With Objective Response (OR) | 0 participants |
Secondary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Population: Data was not analyzed, as study was terminated due to business reasons.
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Population: Data was not analyzed, as study was terminated due to business reasons.