Ovarian Neoplasms, Non-Small-Cell Lung Carcinoma, Melanoma, Other Solid Tumors
Conditions
Keywords
LTT462, ERK, MAPK, solid tumor
Brief summary
A phase I study of LTT462 in patients with advanced solid tumors that harbor MAPK pathway alterations.
Interventions
DRUGLTT462
ERK Inhibitor
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient (male or female) ≥12 years of age * ECOG (Eastern Cooperative Oncology Group) performance status ≤1 * Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate. * Patients must be willing and able to undergo study required biopsies. * Presence of at least one measurable lesion according to RECIST v1.1. * Documented MAPK pathway alteration
Exclusion criteria
* Prior treatment with ERK inhibitors. * History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO. * Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures. * Patients receiving proton pump inhibitors (PPI) which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study. * Patients with malignant disease other than that being treated in the study. * Clinically significant cardiac disease. Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 2.8 years | An adverse events is defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions that occur after participant's signed informed consent has been obtained. A SAE is described as any adverse event that leads to death, is life threatening, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above. |
| Percentage of Participants With Dose Limiting Toxicities (DLTs) | Up to 2.8 years | Percentage of participants with dose limiting toxicity were reported. |
| Percentage of Participants With at Least One Dose Reduction | Up to 2.8 years | Percentage of participants with at least one dose reduction were reported. |
| Percentage of Participants With at Least One Dose Interruptions | Up to 2.8 years | Percentage of participants with at least dose interruptions were reported. |
| Dose Intensity Received by Participants | Up to 2.8 years | Dose intensity of LTT462 received by treatment group was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) - Only for Dose Expansion Phase | Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years) | Median time for overall survival, only for dose expansion phase was reported. |
| The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | day 1, day 15 | Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration expressed in mass x volume-1. |
| The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | day 1, day 15 | Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration. |
| Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462 | Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1 | AUClast is the area under the curve from time zero to the last measurable concentration sampling time calculated by mass \* time \*volume\^-1 |
| The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462 | Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1 | AUCtau is the area under the curve calculated to the end of a dosing interval (tau) at steady-state calculated by formula amount \*time \* volume\^-1 |
| Accumulation Ratio (Racc) of LTT462 | Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1 | Racc is the accumulation ratio calculated by AUCtau ratio Day 15 versus Day 1. |
| Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Cycle 1 Days 1, 2, 3, 15 and 16 | Assessment of Pharmacodynamic (PD) effects of LTT462 in tumor, pre- and post- treatment tumor biopsies were examined for expression of DUSP6. For assessment of PD effects in blood, levels of DUSP6 were measured in blood samples. |
| Elimination Half-life (T1/2) of LTT462 | Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1 | T1/2 is the Elimination half-life. |
| Percentage of Participants With Overall Response Rate (ORR) | Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years) | Percentage of participants with overall response rate were reported. |
| Percentage of Participants With Disease Control Rate (DCR) | Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years) | Percentage of participants with disease control rate were reported. |
| Duration of Response (DOR) | Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years) | DOR is defined as the time between the date of the first documented response (complete response \[CR\] or partial response \[PR\]) and the date of progression. |
| Progression Free Survival (PFS) | Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years) | Median time for progression free survival was reported. |
Countries
Germany, Japan, Singapore, Spain, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LTT462 45 mg QD Participants received 45 mg LTT462 once QD as oral capsules. | 2 |
| LTT462 100 mg QD Participants received 100 mg LTT462 QD as oral capsules. | 3 |
| LTT462 150 mg QD Participants received 150 mg LTT462 QD as oral capsules. | 6 |
| LTT462 200 mg QD Participants received 200 mg LTT462 QD as oral capsules. | 4 |
| LTT462 300 mg QD Participants received 300 mg LTT462 QD as oral capsules. | 8 |
| LTT462 400 mg QD Participants received 400 mg LTT462 QD as oral capsules. | 6 |
| LTT462 450 mg QD Participants received 450 mg LTT462 QD as oral capsules. | 12 |
| LTT462 600 mg QD Participants received 600 mg LTT462 QD as oral capsules. | 6 |
| LTT462 150 mg BID Participants received 150 mg LTT462 BID as oral capsules. | 6 |
| LTT462 200 mg BID Participants received 200 mg LTT462 BID as oral capsules. | 12 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 1 | 2 | 1 | 0 | 0 | 2 |
| Overall Study | Death | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Progressive disease | 1 | 3 | 5 | 3 | 7 | 2 | 8 | 4 | 5 | 6 |
| Overall Study | Subject/guardian decision | 0 | 0 | 0 | 0 | 0 | 2 | 3 | 1 | 0 | 4 |
Baseline characteristics
| Characteristic | LTT462 45 mg QD | LTT462 100 mg QD | LTT462 150 mg QD | LTT462 200 mg QD | LTT462 300 mg QD | LTT462 400 mg QD | LTT462 450 mg QD | LTT462 600 mg QD | LTT462 150 mg BID | LTT462 200 mg BID | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 5 Participants | 1 Participants | 1 Participants | 6 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 5 Participants | 3 Participants | 5 Participants | 5 Participants | 7 Participants | 5 Participants | 5 Participants | 6 Participants | 44 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 4 Participants | 0 Participants | 0 Participants | 2 Participants | 14 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Caucasian | 1 Participants | 2 Participants | 5 Participants | 2 Participants | 6 Participants | 2 Participants | 7 Participants | 4 Participants | 5 Participants | 8 Participants | 42 Participants |
| Race/Ethnicity, Customized Unknown | 00 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 6 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 4 Participants | 2 Participants | 6 Participants | 4 Participants | 5 Participants | 4 Participants | 4 Participants | 7 Participants | 40 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 7 Participants | 2 Participants | 2 Participants | 5 Participants | 25 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 | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 0 / 3 | 0 / 6 | 0 / 4 | 2 / 8 | 1 / 6 | 1 / 12 | 1 / 6 | 6 / 47 | 1 / 6 | 0 / 12 | 1 / 18 |
| other Total, other adverse events | 2 / 2 | 3 / 3 | 6 / 6 | 4 / 4 | 8 / 8 | 6 / 6 | 12 / 12 | 5 / 6 | 46 / 47 | 6 / 6 | 12 / 12 | 18 / 18 |
| serious Total, serious adverse events | 1 / 2 | 0 / 3 | 3 / 6 | 1 / 4 | 5 / 8 | 1 / 6 | 8 / 12 | 4 / 6 | 23 / 47 | 3 / 6 | 5 / 12 | 8 / 18 |
Outcome results
Primary
Dose Intensity Received by Participants
Dose intensity of LTT462 received by treatment group was reported.
Time frame: Up to 2.8 years
Population: The safety set included all participants who had received at least one dose of LTT462.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LTT462 45 mg QD | Dose Intensity Received by Participants | 65.3 milligram per day (mg/day) | Standard Deviation 28.74 |
| LTT462 100 mg QD | Dose Intensity Received by Participants | 98.1 milligram per day (mg/day) | Standard Deviation 3.21 |
| LTT462 150 mg QD | Dose Intensity Received by Participants | 133.9 milligram per day (mg/day) | Standard Deviation 21.84 |
| LTT462 200 mg QD | Dose Intensity Received by Participants | 200.0 milligram per day (mg/day) | Standard Deviation 0 |
| LTT462 300 mg QD | Dose Intensity Received by Participants | 272.7 milligram per day (mg/day) | Standard Deviation 30.9 |
| LTT462 400 mg QD | Dose Intensity Received by Participants | 326.7 milligram per day (mg/day) | Standard Deviation 81.54 |
| LTT462 450 mg QD | Dose Intensity Received by Participants | 409.2 milligram per day (mg/day) | Standard Deviation 64.88 |
| LTT462 600 mg QD | Dose Intensity Received by Participants | 468.2 milligram per day (mg/day) | Standard Deviation 171.48 |
| LTT462 150 mg BID | Dose Intensity Received by Participants | 131.6 milligram per day (mg/day) | Standard Deviation 22.08 |
| LTT462 200 mg BID | Dose Intensity Received by Participants | 178.0 milligram per day (mg/day) | Standard Deviation 35.32 |
Primary
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An adverse events is defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions that occur after participant's signed informed consent has been obtained. A SAE is described as any adverse event that leads to death, is life threatening, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.
Time frame: Up to 2.8 years
Population: The safety set included all participants who had received at least one dose of LTT462.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LTT462 45 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Percentage of participants |
| LTT462 45 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 Percentage of participants |
| LTT462 100 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 Percentage of participants |
| LTT462 100 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Percentage of participants |
| LTT462 150 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 Percentage of participants |
| LTT462 150 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 3 Percentage of participants |
| LTT462 200 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 4 Percentage of participants |
| LTT462 200 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 Percentage of participants |
| LTT462 300 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 5 Percentage of participants |
| LTT462 300 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 8 Percentage of participants |
| LTT462 400 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 Percentage of participants |
| LTT462 400 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 Percentage of participants |
| LTT462 450 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 8 Percentage of participants |
| LTT462 450 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 12 Percentage of participants |
| LTT462 600 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 5 Percentage of participants |
| LTT462 600 mg QD | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 4 Percentage of participants |
| LTT462 150 mg BID | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 Percentage of participants |
| LTT462 150 mg BID | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 3 Percentage of participants |
| LTT462 200 mg BID | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 12 Percentage of participants |
| LTT462 200 mg BID | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 5 Percentage of participants |
Primary
Percentage of Participants With at Least One Dose Interruptions
Percentage of participants with at least dose interruptions were reported.
Time frame: Up to 2.8 years
Population: The safety set included all participants who had received at least one dose of LTT462.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LTT462 45 mg QD | Percentage of Participants With at Least One Dose Interruptions | 100 Percentage of participants |
| LTT462 100 mg QD | Percentage of Participants With at Least One Dose Interruptions | 100 Percentage of participants |
| LTT462 150 mg QD | Percentage of Participants With at Least One Dose Interruptions | 100 Percentage of participants |
| LTT462 200 mg QD | Percentage of Participants With at Least One Dose Interruptions | 100 Percentage of participants |
| LTT462 300 mg QD | Percentage of Participants With at Least One Dose Interruptions | 100 Percentage of participants |
| LTT462 400 mg QD | Percentage of Participants With at Least One Dose Interruptions | 100 Percentage of participants |
| LTT462 450 mg QD | Percentage of Participants With at Least One Dose Interruptions | 100 Percentage of participants |
| LTT462 600 mg QD | Percentage of Participants With at Least One Dose Interruptions | 100 Percentage of participants |
| LTT462 150 mg BID | Percentage of Participants With at Least One Dose Interruptions | 100 Percentage of participants |
| LTT462 200 mg BID | Percentage of Participants With at Least One Dose Interruptions | 100 Percentage of participants |
Primary
Percentage of Participants With at Least One Dose Reduction
Percentage of participants with at least one dose reduction were reported.
Time frame: Up to 2.8 years
Population: The safety set included all participants who had received at least one dose of LTT462.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LTT462 45 mg QD | Percentage of Participants With at Least One Dose Reduction | 0 Percentage of participants |
| LTT462 100 mg QD | Percentage of Participants With at Least One Dose Reduction | 0 Percentage of participants |
| LTT462 150 mg QD | Percentage of Participants With at Least One Dose Reduction | 16.7 Percentage of participants |
| LTT462 200 mg QD | Percentage of Participants With at Least One Dose Reduction | 0 Percentage of participants |
| LTT462 300 mg QD | Percentage of Participants With at Least One Dose Reduction | 0 Percentage of participants |
| LTT462 400 mg QD | Percentage of Participants With at Least One Dose Reduction | 0 Percentage of participants |
| LTT462 450 mg QD | Percentage of Participants With at Least One Dose Reduction | 16.7 Percentage of participants |
| LTT462 600 mg QD | Percentage of Participants With at Least One Dose Reduction | 33.3 Percentage of participants |
| LTT462 150 mg BID | Percentage of Participants With at Least One Dose Reduction | 16.7 Percentage of participants |
| LTT462 200 mg BID | Percentage of Participants With at Least One Dose Reduction | 33.3 Percentage of participants |
Primary
Percentage of Participants With Dose Limiting Toxicities (DLTs)
Percentage of participants with dose limiting toxicity were reported.
Time frame: Up to 2.8 years
Population: The dose determining set included all participants from the safety set enrolled in the escalation part of the study who, during the first 28 days of dosing, had received at least 75 percent of the planned daily doses of LTT462 and had had sufficient safety evaluations, or had experienced a DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LTT462 45 mg QD | Percentage of Participants With Dose Limiting Toxicities (DLTs) | 0 Percentage of participants |
| LTT462 100 mg QD | Percentage of Participants With Dose Limiting Toxicities (DLTs) | 0 Percentage of participants |
| LTT462 150 mg QD | Percentage of Participants With Dose Limiting Toxicities (DLTs) | 16.7 Percentage of participants |
| LTT462 200 mg QD | Percentage of Participants With Dose Limiting Toxicities (DLTs) | 25.0 Percentage of participants |
| LTT462 300 mg QD | Percentage of Participants With Dose Limiting Toxicities (DLTs) | 0 Percentage of participants |
| LTT462 400 mg QD | Percentage of Participants With Dose Limiting Toxicities (DLTs) | 0 Percentage of participants |
| LTT462 450 mg QD | Percentage of Participants With Dose Limiting Toxicities (DLTs) | 28.6 Percentage of participants |
| LTT462 600 mg QD | Percentage of Participants With Dose Limiting Toxicities (DLTs) | 100 Percentage of participants |
| LTT462 150 mg BID | Percentage of Participants With Dose Limiting Toxicities (DLTs) | 0 Percentage of participants |
| LTT462 200 mg BID | Percentage of Participants With Dose Limiting Toxicities (DLTs) | 44.4 Percentage of participants |
Secondary
Accumulation Ratio (Racc) of LTT462
Racc is the accumulation ratio calculated by AUCtau ratio Day 15 versus Day 1.
Time frame: Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Population: PAS included of all participants who have at least 1 PK blood sample providing measurable LTT462 and received at least 1 dose of study drug, didn't vomit within 4 hours postdose, had at least 1 primary PK parameter. Here 'N' number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LTT462 45 mg QD | Accumulation Ratio (Racc) of LTT462 | 3.01 Ratio | — |
| LTT462 100 mg QD | Accumulation Ratio (Racc) of LTT462 | 3.35 Ratio | — |
| LTT462 150 mg QD | Accumulation Ratio (Racc) of LTT462 | 5.09 Ratio | Geometric Coefficient of Variation 72.7 |
| LTT462 200 mg QD | Accumulation Ratio (Racc) of LTT462 | 2.74 Ratio | Geometric Coefficient of Variation 46.9 |
| LTT462 300 mg QD | Accumulation Ratio (Racc) of LTT462 | 1.49 Ratio | Geometric Coefficient of Variation 25.1 |
| LTT462 400 mg QD | Accumulation Ratio (Racc) of LTT462 | 1.73 Ratio | Geometric Coefficient of Variation 62.4 |
| LTT462 450 mg QD | Accumulation Ratio (Racc) of LTT462 | 1.44 Ratio | Geometric Coefficient of Variation 73.4 |
| LTT462 150 mg BID | Accumulation Ratio (Racc) of LTT462 | 3.19 Ratio | Geometric Coefficient of Variation 50.2 |
| LTT462 200 mg BID | Accumulation Ratio (Racc) of LTT462 | 6.89 Ratio | Geometric Coefficient of Variation 84.3 |
Secondary
Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462
AUClast is the area under the curve from time zero to the last measurable concentration sampling time calculated by mass \* time \*volume\^-1
Time frame: Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Population: PAS included of all participants who have at least 1 PK blood sample providing measurable LTT462 and received at least 1 dose of study drug, didn't vomit within 4 hours postdose, had at least 1 primary PK parameter. Here 'N' number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LTT462 45 mg QD | Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462 | 851 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 106 |
| LTT462 100 mg QD | Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462 | 2260 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 30 |
| LTT462 150 mg QD | Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462 | 3880 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 133.6 |
| LTT462 200 mg QD | Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462 | 10400 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 95.4 |
| LTT462 300 mg QD | Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462 | 12800 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 157.4 |
| LTT462 400 mg QD | Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462 | 23300 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 55.5 |
| LTT462 450 mg QD | Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462 | 23800 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 115.3 |
| LTT462 600 mg QD | Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462 | 11800 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 64.2 |
| LTT462 150 mg BID | Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462 | 9240 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 78.3 |
| LTT462 200 mg BID | Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462 | 7630 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 98.8 |
Secondary
Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood
Assessment of Pharmacodynamic (PD) effects of LTT462 in tumor, pre- and post- treatment tumor biopsies were examined for expression of DUSP6. For assessment of PD effects in blood, levels of DUSP6 were measured in blood samples.
Time frame: Cycle 1 Days 1, 2, 3, 15 and 16
Population: The full analysis set included all participants who had received at least one dose of LTT462.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LTT462 45 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Tumor Sample | -0.2 Ratio | — |
| LTT462 45 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Blood Sample | -50.8 Ratio | Standard Deviation 6.14 |
| LTT462 100 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Tumor Sample | 0.8 Ratio | Standard Deviation 1.11 |
| LTT462 100 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Blood Sample | -66.1 Ratio | Standard Deviation 40.22 |
| LTT462 150 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Tumor Sample | -1.1 Ratio | Standard Deviation 29.46 |
| LTT462 150 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Blood Sample | -35.2 Ratio | Standard Deviation 27.33 |
| LTT462 200 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Tumor Sample | -28.8 Ratio | — |
| LTT462 200 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Blood Sample | -34.7 Ratio | Standard Deviation 22.02 |
| LTT462 300 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Blood Sample | -42.5 Ratio | Standard Deviation 16.56 |
| LTT462 300 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Tumor Sample | -31.0 Ratio | Standard Deviation 31.06 |
| LTT462 400 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Blood Sample | -43.0 Ratio | Standard Deviation 13.67 |
| LTT462 400 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Tumor Sample | -56.5 Ratio | — |
| LTT462 450 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Blood Sample | -40.1 Ratio | Standard Deviation 9.92 |
| LTT462 450 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Tumor Sample | -22.2 Ratio | Standard Deviation 28.67 |
| LTT462 600 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Tumor Sample | -79.9 Ratio | — |
| LTT462 600 mg QD | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Blood Sample | -40.4 Ratio | Standard Deviation 21.04 |
| LTT462 150 mg BID | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Tumor Sample | -61.8 Ratio | Standard Deviation 4.16 |
| LTT462 150 mg BID | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Blood Sample | -39.2 Ratio | Standard Deviation 12.98 |
| LTT462 200 mg BID | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Tumor Sample | -14.4 Ratio | Standard Deviation 22.27 |
| LTT462 200 mg BID | Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood | Blood Sample | -32.9 Ratio | Standard Deviation 18.71 |
Secondary
Duration of Response (DOR)
DOR is defined as the time between the date of the first documented response (complete response \[CR\] or partial response \[PR\]) and the date of progression.
Time frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Population: As there were no participant achieving response (CR or PR) during escalation phase of the study (only stable disease was achieved). Therefore the evaluation of duration of response could not be performed.
Secondary
Elimination Half-life (T1/2) of LTT462
T1/2 is the Elimination half-life.
Time frame: Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Population: PAS included of all participants who have at least 1 PK blood sample providing measurable LTT462 and received at least 1 dose of study drug, didn't vomit within 4 hours postdose, had at least 1 primary PK parameter. Here 'N' number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LTT462 45 mg QD | Elimination Half-life (T1/2) of LTT462 | 27.9 hour |
| LTT462 100 mg QD | Elimination Half-life (T1/2) of LTT462 | 39.2 hour |
| LTT462 150 mg QD | Elimination Half-life (T1/2) of LTT462 | 20.8 hour |
| LTT462 200 mg QD | Elimination Half-life (T1/2) of LTT462 | 16.8 hour |
| LTT462 300 mg QD | Elimination Half-life (T1/2) of LTT462 | 15.2 hour |
| LTT462 400 mg QD | Elimination Half-life (T1/2) of LTT462 | 14.0 hour |
| LTT462 450 mg QD | Elimination Half-life (T1/2) of LTT462 | 17.6 hour |
| LTT462 600 mg QD | Elimination Half-life (T1/2) of LTT462 | 13.2 hour |
| LTT462 150 mg BID | Elimination Half-life (T1/2) of LTT462 | 16.2 hour |
| LTT462 200 mg BID | Elimination Half-life (T1/2) of LTT462 | 17.1 hour |
Secondary
Overall Survival (OS) - Only for Dose Expansion Phase
Median time for overall survival, only for dose expansion phase was reported.
Time frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Population: Overall survival was not evaluated because the study ended before enrolling into the dose-expansion part.
Secondary
Percentage of Participants With Disease Control Rate (DCR)
Percentage of participants with disease control rate were reported.
Time frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Population: The full analysis set included all participants who had received at least one dose of LTT462.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LTT462 45 mg QD | Percentage of Participants With Disease Control Rate (DCR) | 50.0 Percentage of participants |
| LTT462 100 mg QD | Percentage of Participants With Disease Control Rate (DCR) | 0 Percentage of participants |
| LTT462 150 mg QD | Percentage of Participants With Disease Control Rate (DCR) | 0 Percentage of participants |
| LTT462 200 mg QD | Percentage of Participants With Disease Control Rate (DCR) | 0 Percentage of participants |
| LTT462 300 mg QD | Percentage of Participants With Disease Control Rate (DCR) | 37.5 Percentage of participants |
| LTT462 400 mg QD | Percentage of Participants With Disease Control Rate (DCR) | 16.7 Percentage of participants |
| LTT462 450 mg QD | Percentage of Participants With Disease Control Rate (DCR) | 8.3 Percentage of participants |
| LTT462 600 mg QD | Percentage of Participants With Disease Control Rate (DCR) | 16.7 Percentage of participants |
| LTT462 150 mg BID | Percentage of Participants With Disease Control Rate (DCR) | 16.7 Percentage of participants |
| LTT462 200 mg BID | Percentage of Participants With Disease Control Rate (DCR) | 0 Percentage of participants |
Secondary
Percentage of Participants With Overall Response Rate (ORR)
Percentage of participants with overall response rate were reported.
Time frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Population: The full analysis set included all participants who had received at least one dose of LTT462.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LTT462 45 mg QD | Percentage of Participants With Overall Response Rate (ORR) | 0 Percentage of participants |
| LTT462 100 mg QD | Percentage of Participants With Overall Response Rate (ORR) | 0 Percentage of participants |
| LTT462 150 mg QD | Percentage of Participants With Overall Response Rate (ORR) | 0 Percentage of participants |
| LTT462 200 mg QD | Percentage of Participants With Overall Response Rate (ORR) | 0 Percentage of participants |
| LTT462 300 mg QD | Percentage of Participants With Overall Response Rate (ORR) | 0 Percentage of participants |
| LTT462 400 mg QD | Percentage of Participants With Overall Response Rate (ORR) | 0 Percentage of participants |
| LTT462 450 mg QD | Percentage of Participants With Overall Response Rate (ORR) | 0 Percentage of participants |
| LTT462 600 mg QD | Percentage of Participants With Overall Response Rate (ORR) | 0 Percentage of participants |
| LTT462 150 mg BID | Percentage of Participants With Overall Response Rate (ORR) | 0 Percentage of participants |
| LTT462 200 mg BID | Percentage of Participants With Overall Response Rate (ORR) | 0 Percentage of participants |
Secondary
Progression Free Survival (PFS)
Median time for progression free survival was reported.
Time frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Population: The full analysis set included all participants who had received at least one dose of LTT462.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LTT462 45 mg QD | Progression Free Survival (PFS) | 5.3 months |
| LTT462 100 mg QD | Progression Free Survival (PFS) | 1.6 months |
| LTT462 150 mg QD | Progression Free Survival (PFS) | 1.7 months |
| LTT462 200 mg QD | Progression Free Survival (PFS) | 1.9 months |
| LTT462 300 mg QD | Progression Free Survival (PFS) | 1.8 months |
| LTT462 400 mg QD | Progression Free Survival (PFS) | 2.1 months |
| LTT462 450 mg QD | Progression Free Survival (PFS) | 0.9 months |
| LTT462 600 mg QD | Progression Free Survival (PFS) | 1.4 months |
| LTT462 150 mg BID | Progression Free Survival (PFS) | 1.5 months |
| LTT462 200 mg BID | Progression Free Survival (PFS) | 1.6 months |
Secondary
The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462
AUCtau is the area under the curve calculated to the end of a dosing interval (tau) at steady-state calculated by formula amount \*time \* volume\^-1
Time frame: Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Population: PAS included of all participants who have at least 1 PK blood sample providing measurable LTT462 and received at least 1 dose of study drug, didn't vomit within 4 hours postdose, had at least 1 primary PK parameter. Here 'N' number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LTT462 45 mg QD | The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462 | 3010 h*ng/mL | — |
| LTT462 100 mg QD | The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462 | 6370 h*ng/mL | — |
| LTT462 150 mg QD | The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462 | 8660 h*ng/mL | Geometric Coefficient of Variation 50 |
| LTT462 200 mg QD | The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462 | 14600 h*ng/mL | Geometric Coefficient of Variation 96.5 |
| LTT462 300 mg QD | The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462 | 13100 h*ng/mL | Geometric Coefficient of Variation 81.6 |
| LTT462 400 mg QD | The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462 | 25400 h*ng/mL | Geometric Coefficient of Variation 74.3 |
| LTT462 450 mg QD | The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462 | 35400 h*ng/mL | Geometric Coefficient of Variation 94.8 |
| LTT462 600 mg QD | The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462 | 6760 h*ng/mL | — |
| LTT462 150 mg BID | The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462 | 11100 h*ng/mL | Geometric Coefficient of Variation 59.5 |
| LTT462 200 mg BID | The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462 | 18600 h*ng/mL | Geometric Coefficient of Variation 85.2 |
Secondary
The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462
Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration expressed in mass x volume-1.
Time frame: day 1, day 15
Population: Pharmacokinetic (PK) analysis set (PAS) included of all participants who have at least 1 PK blood sample providing measurable LTT462 and received at least 1 dose of study drug, didn't vomit within 4 hours postdose, had at least 1 primary PK parameter. Here 'n' number analyzed signifies number of participants who were evaluable at each time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LTT462 45 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 1 | 61.3 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 55.9 |
| LTT462 45 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 15 | 139 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 29.9 |
| LTT462 100 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 1 | 134 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38.8 |
| LTT462 100 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 15 | 938 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 82.5 |
| LTT462 150 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 1 | 218 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 230.9 |
| LTT462 150 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 15 | 707 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 69 |
| LTT462 200 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 1 | 494 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 126.8 |
| LTT462 200 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 15 | 972 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 92.4 |
| LTT462 300 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 15 | 1330 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 131.9 |
| LTT462 300 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 1 | 717 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 127.4 |
| LTT462 400 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 15 | 2370 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 83.3 |
| LTT462 400 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 1 | 1580 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 60.8 |
| LTT462 450 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 15 | 3470 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 49.7 |
| LTT462 450 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 1 | 1420 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 83.5 |
| LTT462 600 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 1 | 1280 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 47.7 |
| LTT462 600 mg QD | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 15 | 1030 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 248.8 |
| LTT462 150 mg BID | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 1 | 598 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 83 |
| LTT462 150 mg BID | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 15 | 1390 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 58.5 |
| LTT462 200 mg BID | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 1 | 575 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 73.8 |
| LTT462 200 mg BID | The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 | Day 15 | 1510 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 108 |
Secondary
The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462
Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration.
Time frame: day 1, day 15
Population: PAS included of all participants who have at least 1 PK blood sample providing measurable LTT462 and received at least 1 dose of study drug, didn't vomit within 4 hours postdose, had at least 1 primary PK parameter. Here 'n' number analyzed signifies number of participants who were evaluable at each time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LTT462 45 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 1 | 2.45 hour |
| LTT462 45 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 15 | 5.93 hour |
| LTT462 100 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 1 | 1.98 hour |
| LTT462 100 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 15 | 4.02 hour |
| LTT462 150 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 1 | 3.49 hour |
| LTT462 150 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 15 | 4.05 hour |
| LTT462 200 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 1 | 5.48 hour |
| LTT462 200 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 15 | 3.00 hour |
| LTT462 300 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 15 | 2.59 hour |
| LTT462 300 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 1 | 3.08 hour |
| LTT462 400 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 15 | 2.55 hour |
| LTT462 400 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 1 | 3.04 hour |
| LTT462 450 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 15 | 2.98 hour |
| LTT462 450 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 1 | 3.98 hour |
| LTT462 600 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 1 | 3.95 hour |
| LTT462 600 mg QD | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 15 | 5.25 hour |
| LTT462 150 mg BID | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 1 | 2.25 hour |
| LTT462 150 mg BID | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 15 | 2.17 hour |
| LTT462 200 mg BID | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 1 | 3.03 hour |
| LTT462 200 mg BID | The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 | Day 15 | 2.18 hour |