Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to find a safe and tolerable dose of Lipotecan® when administered to patients with advanced solid tumors.
Lipotecan® is a drug product of TLC388 HCl, which is a potent camptothecin analog with cytotoxic activities against a variety of human tumor cell lines in vitro and anti-tumor activities in several xenograft models with human tumor cell lines. Structurally, TLC388 HCl is related to other camptothecins, but it has been chemically modified to improve stability and potency, and to minimize toxicities.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lipotecan | Experimental | Intravenous Lipotecan (TLC388 HCl for Injection) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lipotecan | Drug | Lipotecan IV day 1, 8, 15 |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Lipotecan | MTD is the highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity (DLT)). A 3+3 study design was used to determine MTD. The MTD was the highest dose level at which 0 of 3 or 1 of 6 patients experience a DLT, with the next higher dose having at least 2 of 3 or 2 of 6 patients experiencing a DLT. | First treatment to toxicity up to 42 days |
| Number of Participants With Adverse Events | Number of participants with AEs that occurred during treatment and follow-up period (30 days after last treatment). Drug-related AEs and SAEs were followed until resolved or stabilized. AEs were classified by the investigator according to severity graded using CTCAE version 3.0 and relationship to study drug. The severity scale is: Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening or disabling, Grade 5= Death related to AE | an average of 6 months |
| Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,R-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,S-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Maximum Observed Dose-normalized Plasma Concentration (Cmax) of Topotecan | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. |
| Measure | Description | Time Frame |
|---|---|---|
| Anti-tumor Activity | Patients were evaluated by tumor assessment using RECIST guidelines. Possible evaluations include: Complete Response (CR): disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the size of target lesions. Progressive Disease (PD): at least a 20% increase in the size of target lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Min-Hsiung Kao | Taiwan Liposome Company, Ltd. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical College of Georgia | Augusta | Georgia | 30912 | United States | ||
| Bidmc, Dfci, Mgh |
Patients will attend the clinic for a screening visit up to 28 days before receiving, if eligible, the first dose of Lipotecan®.
The study recruitment period was from Sep 2008 to Dec 2010. Patients were recruited from three US clinical sites and one Taiwan site.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 (1.5 mg/m^2) | Participants received 1.5 mg/m^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study. |
| FG001 | Cohort 2 (3 mg/m^2) | Participants received 3 mg/m^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study. |
| FG002 | Cohort 3 (6 mg/m^2) | Participants received 6 mg/m^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study. |
| FG003 | Cohort 4 (9 mg/m^2) | Participants received 9 mg/m^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study. |
| FG004 | Cohort 5 (13.5 mg/m^2) | Participants received 13.5 mg/m^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study. |
| FG005 | Cohort 6 (20 mg/m^2) | Participants received 20 mg/m^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study. |
| FG006 | Cohort 7 (30 mg/m^2) | Participants received 30 mg/m^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study. |
| FG007 | Cohort 8 (40 mg/m^2) | Participants received 40 mg/m^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study. |
| FG008 | Cohort 9 (35 mg/m^2) | Participants received 35 mg/m^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study. |
| FG009 | Cohort 10 (40 mg/m^2) | Participants received 40 mg/m^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study. |
| FG010 | Cohort 11 (50 mg/m^2) | Participants received 50 mg/m^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study. |
| FG011 | Cohort 12 (60 mg/m^2) | Participants received 60 mg/m^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cohort 1 (1.5 mg/m^2) Period |
| |||||||||||||
| Cohort 2 (3 mg/m^2) Period |
| |||||||||||||
| Cohort 3 (6 mg/m^2) Period |
| |||||||||||||
| Cohort 4 (9 mg/m^2) Period |
| |||||||||||||
| Cohort 5 (13.5 mg/m^2) Period |
| |||||||||||||
| Cohort 6 (20 mg/m^2) Period |
| |||||||||||||
| Cohort 7 (30 mg/m^2) Period |
| |||||||||||||
| Cohort 8 (40 mg/m^2) Period |
| |||||||||||||
| Cohort 9 (35 mg/m^2) Period |
| |||||||||||||
| Cohort 10 (40 mg/m^2) Period |
| |||||||||||||
| Cohort 11 (50 mg/m^2) Period |
| |||||||||||||
| Cohort 12 (60 mg/m^2) Period |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Overall Population | Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Tolerated Dose (MTD) of Lipotecan | MTD is the highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity (DLT)). A 3+3 study design was used to determine MTD. The MTD was the highest dose level at which 0 of 3 or 1 of 6 patients experience a DLT, with the next higher dose having at least 2 of 3 or 2 of 6 patients experiencing a DLT. | Patients received at least one dose of Lipotecan. | Posted | Number | mg/m^2 | First treatment to toxicity up to 42 days |
|
32 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Overall Population | Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ABDOMINAL DISTENSION | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Shu Chi Hsu | Taiwan Liposome Company, Ltd. | 650-872-8816 | 102 | shuchi@tlcbio.com |
Not provided
| ID | Term |
|---|---|
| C549429 | TLC 388 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U1 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U2 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1h, 1h30m, 2h, 4h, 8h |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,R-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,S-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Topotecan | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U1 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U2 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,R-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,S-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Topotecan | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U1 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U2 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Plasma Decay Half-Life (t1/2) of S,R-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Plasma Decay Half-Life (t1/2) of S,S-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Plasma Decay Half-Life (t1/2) of Topotecan | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Plasma Decay Half-Life (t1/2) of TLC-U1 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| Plasma Decay Half-Life (t1/2) of TLC-U2 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
| From start of treatment assessed every 2 cycles up to 2.5 years |
| Boston |
| Massachusetts |
| 02215 |
| United States |
| Montefiore Medical Center | The Bronx | New York | 10461 | United States |
| National Taiwan University Hospital | Taipei | Taiwan |
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Secondary | Anti-tumor Activity | Patients were evaluated by tumor assessment using RECIST guidelines. Possible evaluations include: Complete Response (CR): disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the size of target lesions. Progressive Disease (PD): at least a 20% increase in the size of target lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. | Patients received at least one dose of Lipotecan. | Posted | Number | participants | From start of treatment assessed every 2 cycles up to 2.5 years |
|
|
|
| Primary | Number of Participants With Adverse Events | Number of participants with AEs that occurred during treatment and follow-up period (30 days after last treatment). Drug-related AEs and SAEs were followed until resolved or stabilized. AEs were classified by the investigator according to severity graded using CTCAE version 3.0 and relationship to study drug. The severity scale is: Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening or disabling, Grade 5= Death related to AE | Patients received at least one dose of Lipotecan | Posted | Number | participants | an average of 6 months |
|
|
|
| Primary | Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,R-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | ng/mL | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,S-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | ng/mL | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Maximum Observed Dose-normalized Plasma Concentration (Cmax) of Topotecan | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | ng/mL | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U1 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | ng/mL | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U2 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | ng/mL | 0, 15m, 29m, 33m, 40m, 50m, 1h, 1h30m, 2h, 4h, 8h |
|
|
|
| Primary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,R-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hour | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h |
|
|
|
| Primary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,S-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hour | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Topotecan | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hour | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U1 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hour | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U2 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hour | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,R-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hr*ng/mL | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,S-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hr*ng/mL | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Topotecan | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hr*ng/mL | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U1 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hr*ng/mL | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U2 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hr*ng/mL | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Plasma Decay Half-Life (t1/2) of S,R-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hour | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Plasma Decay Half-Life (t1/2) of S,S-TLC388 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hour | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Plasma Decay Half-Life (t1/2) of Topotecan | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hour | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Plasma Decay Half-Life (t1/2) of TLC-U1 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hour | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| Primary | Plasma Decay Half-Life (t1/2) of TLC-U2 | Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human. | Patients complete cycle 1 and 2 treatments without major protocol deviation. | Posted | Mean | Standard Deviation | hour | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose |
|
|
|
| 11 |
| 54 |
| 54 |
| 54 |
| ACUTE MYOCARDIAL INFARCTION | Cardiac disorders | MedDRA (11.1) | Systematic Assessment |
|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
|
| ASTHENIA | General disorders | MedDRA (11.1) | Systematic Assessment |
|
| CARDIO-RESPIRATORY ARREST | Cardiac disorders | MedDRA (11.1) | Systematic Assessment |
|
| CEREBROVASCULAR ACCIDENT | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| CYSTITIS KLEBSIELLA | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| DEHYDRATION | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| ENTEROVESICAL FISTULA | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| ESCHERICHIA URINARY TRACT INFECTION | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| FEBRILE NEUTROPENIA | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
|
| FLANK PAIN | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| HAEMATURIA | Renal and urinary disorders | MedDRA (11.1) | Systematic Assessment |
|
| HYPERTENSION | Vascular disorders | MedDRA (11.1) | Systematic Assessment |
|
| HYPONATRAEMIA | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| LEUKOPENIA | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
|
| NEUTROPENIA | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
|
| PYELONEPHRITIS | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| THROMBOCYTOPENIA | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
|
| URINARY TRACT INFECTION | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA (11.1) | Systematic Assessment |
|
| ALOPECIA | Skin and subcutaneous tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
|
| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| BLOOD ALKALINE PHOSPHATASE INCREASED | Investigations | MedDRA (11.1) | Systematic Assessment |
|
| CONSTIPATION | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| DECREASED APPETITE | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| DIZZINESS | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| FATIGUE | General disorders | MedDRA (11.1) | Systematic Assessment |
|
| FLANK PAIN | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| HYPERCALCAEMIA | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| HYPOALBUMINAEMIA | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| HYPOCALCAEMIA | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| HYPOKALAEMIA | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| HYPONATRAEMIA | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| HYPOPHOSPHATAEMIA | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| HYPOTENSION | Vascular disorders | MedDRA (11.1) | Systematic Assessment |
|
| INSOMNIA | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
|
| INTERNATIONAL NORMALISED RATIO INCREASED | Investigations | MedDRA (11.1) | Systematic Assessment |
|
| LEUKOPENIA | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
|
| MUSCLE SPASMS | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| MUSCULOSKELETAL PAIN | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| NEUTROPENIA | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
|
| OEDEMA PERIPHERAL | General disorders | MedDRA (11.1) | Systematic Assessment |
|
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| PYREXIA | General disorders | MedDRA (11.1) | Systematic Assessment |
|
| THROMBOCYTOPENIA | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
|
| URINARY TRACT INFECTION | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| VOMITING | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| WEIGHT DECREASED | Investigations | MedDRA (11.1) | Systematic Assessment |
|
Not provided
| Title | Measurements |
|---|---|
|
| Progression Disease (PD) |
|
| No assessment |
|