NCT01072175 · OUTCOME
Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites
Investigate Safety, Pharmacokinetics and Pharmacodynamics of GSK2118436 & GSK1120212 · Source last updated 2019-07-05
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- GEOMETRIC_MEAN
- Unit
- ng*hour/mL (ng*hr/mL)
- Interval / dispersion
- 95% Confidence Interval
- Time frame
- Day 15
What was measured
Blood samples for PK analysis of dabrafenib and its metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were obtained at pre-dose and at 1, 2, 3, 4, 6, 8, 10, and 24 hours after dabrafenib administration. AUC is defined as the area under the dabrafenib concentration-time curve as a measure of drug exposure. AUC (0-inf) is defined as the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time. AUC (0-t) is defined as area under the concentration-time curve from time zero (pre-dose) to the last time of quantifiable concentration. Date are reported as geometric least square means.
Analysis population: PK Population
Groups in this outcome
Part A: Dabrafenib 75 mg
Participants received a single dose of dabrafenib 75 mg gelatin capsules alone on Day 1.
Part A: Dabrafenib 75 mg + Trametinib 2 mg
Participants received a single dose of dabrafenib 75 mg gelatin capsules with repeat dose trametinib (Day 15).
Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.
Analysis denominator · Participants
| Group | Source count |
|---|
| Part A: Dabrafenib 75 mg | 8 |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 8 |
|---|
Reported measurements
GSK2118436 AUC (0-t)
Analysis denominator · Participants
| Group | Source count |
|---|
| Part A: Dabrafenib 75 mg | 8 |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 8 |
|---|
Values in ng*hour/mL (ng*hr/mL) · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part A: Dabrafenib 75 mg | 2734 | Not reported | 2205 | 3390 | Not reported |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 2751 | Not reported | 2219 | 3411 | Not reported |
|---|
GSK2118436 AUC (0-inf)
Analysis denominator · Participants
| Group | Source count |
|---|
| Part A: Dabrafenib 75 mg | 8 |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 8 |
|---|
Values in ng*hour/mL (ng*hr/mL) · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part A: Dabrafenib 75 mg | 3128 | Not reported | 2578 | 3797 | Not reported |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 2949 | Not reported | 2445 | 3556 | Not reported |
|---|
GSK2285403 AUC (0-t)
Analysis denominator · Participants
| Group | Source count |
|---|
| Part A: Dabrafenib 75 mg | 8 |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 8 |
|---|
Values in ng*hour/mL (ng*hr/mL) · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part A: Dabrafenib 75 mg | 2232 | Not reported | 1684 | 2959 | Not reported |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 2287 | Not reported | 1899 | 2753 | Not reported |
|---|
GSK2285403 AUC (0-inf)
Analysis denominator · Participants
| Group | Source count |
|---|
| Part A: Dabrafenib 75 mg | 8 |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 8 |
|---|
Values in ng*hour/mL (ng*hr/mL) · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part A: Dabrafenib 75 mg | 2819 | Not reported | 2231 | 3562 | Not reported |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 2497 | Not reported | 2097 | 2974 | Not reported |
|---|
GSK2298683 AUC (0-t)
Analysis denominator · Participants
| Group | Source count |
|---|
| Part A: Dabrafenib 75 mg | 8 |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 8 |
|---|
Values in ng*hour/mL (ng*hr/mL) · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part A: Dabrafenib 75 mg | 12761 | Not reported | 10347 | 15738 | Not reported |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 13053 | Not reported | 10475 | 16266 | Not reported |
|---|
GSK2298683 AUC (0-inf)
Analysis denominator · Participants
| Group | Source count |
|---|
| Part A: Dabrafenib 75 mg | 0 |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 0 |
|---|
GSK2167542 AUC (0-t)
Analysis denominator · Participants
| Group | Source count |
|---|
| Part A: Dabrafenib 75 mg | 8 |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 8 |
|---|
Values in ng*hour/mL (ng*hr/mL) · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part A: Dabrafenib 75 mg | 270 | Not reported | 188 | 390 | Not reported |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 276 | Not reported | 230 | 332 | Not reported |
|---|
GSK2167542 AUC (0-inf)
Analysis denominator · Participants
| Group | Source count |
|---|
| Part A: Dabrafenib 75 mg | 0 |
|---|
| Part A: Dabrafenib 75 mg + Trametinib 2 mg | 0 |
|---|
Source statistical analyses
Group order, estimate direction, methods and comments are retained. No treatment ranking is inferred.
- ci Lower Limit
- 0.85
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 1.19
- estimate Comment
- Geometric mean ratio (Day 15 AUC(0-inf)/ Day 1 AUC(0-inf)) and 90% confidence interval for dabrafenib were calculated.
- non Inferiority Comment
- AUC(0-t) of dabrafenib was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
- non Inferiority Type
- NON_INFERIORITY_OR_EQUIVALENCE
- param Type
- Geometric Mean Ratio
- param Value
- 1.01
- ci Lower Limit
- 0.82
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 1.08
- estimate Comment
- Geometric mean ratio (Day 15 AUC(0-inf)/ Day 1 AUC(0-inf)) and 90% confidence interval for dabrafenib were calculated.
- non Inferiority Comment
- AUC(0-inf) of dabrafenib was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
- non Inferiority Type
- NON_INFERIORITY_OR_EQUIVALENCE
- param Type
- Geometric Mean Ratio
- param Value
- 0.94
- ci Lower Limit
- 0.84
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 1.25
- estimate Comment
- Geometric mean ratio (Day 15 AUC(0-t)/ Day 1 AUC(0-t)) and 90% confidence interval for GSK2285403 were calculated.
- non Inferiority Comment
- AUC(0-t) of GSK2285403 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
- non Inferiority Type
- NON_INFERIORITY_OR_EQUIVALENCE
- param Type
- Geometric Mean Ratio
- param Value
- 1.02
- ci Lower Limit
- 0.81
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 1.03
- estimate Comment
- Geometric mean ratio (Day 15 AUC(0-inf)/ Day 1 AUC(0-inf)) and 90% confidence interval for GSK2285403 were calculated.
- non Inferiority Comment
- AUC(0-inf) of GSK2285403 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
- non Inferiority Type
- NON_INFERIORITY_OR_EQUIVALENCE
- param Type
- Geometric Mean Ratio
- param Value
- 0.92
- ci Lower Limit
- 0.81
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 1.29
- estimate Comment
- Geometric mean ratio (Day 15 AUC(0-t)/ Day 1 AUC(0-t)) and 90% confidence interval for GSK2298683 were calculated.
- non Inferiority Comment
- AUC(0-t) of GSK2298683 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
- non Inferiority Type
- NON_INFERIORITY_OR_EQUIVALENCE
- param Type
- Geometric Mean Ratio
- param Value
- 1.02
- ci Lower Limit
- 0.76
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 1.37
- estimate Comment
- Geometric mean ratio (Day 15 AUC(0-t)/ Day 1 AUC(0-t)) and 90% confidence interval for GSK2167542 were calculated.
- non Inferiority Comment
- AUC(0-t) of GSK2167542 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
- non Inferiority Type
- NON_INFERIORITY_OR_EQUIVALENCE
- param Type
- Geometric Mean Ratio
- param Value
- 1.02
Complete source fields
- analyses
- ci Lower Limit
- 0.85
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 1.19
- estimate Comment
- Geometric mean ratio (Day 15 AUC(0-inf)/ Day 1 AUC(0-inf)) and 90% confidence interval for dabrafenib were calculated.
- non Inferiority Comment
- AUC(0-t) of dabrafenib was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
- non Inferiority Type
- NON_INFERIORITY_OR_EQUIVALENCE
- param Type
- Geometric Mean Ratio
- param Value
- 1.01
- ci Lower Limit
- 0.82
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 1.08
- estimate Comment
- Geometric mean ratio (Day 15 AUC(0-inf)/ Day 1 AUC(0-inf)) and 90% confidence interval for dabrafenib were calculated.
- non Inferiority Comment
- AUC(0-inf) of dabrafenib was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
- non Inferiority Type
- NON_INFERIORITY_OR_EQUIVALENCE
- param Type
- Geometric Mean Ratio
- param Value
- 0.94
- ci Lower Limit
- 0.84
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 1.25
- estimate Comment
- Geometric mean ratio (Day 15 AUC(0-t)/ Day 1 AUC(0-t)) and 90% confidence interval for GSK2285403 were calculated.
- non Inferiority Comment
- AUC(0-t) of GSK2285403 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
- non Inferiority Type
- NON_INFERIORITY_OR_EQUIVALENCE
- param Type
- Geometric Mean Ratio
- param Value
- 1.02
- ci Lower Limit
- 0.81
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 1.03
- estimate Comment
- Geometric mean ratio (Day 15 AUC(0-inf)/ Day 1 AUC(0-inf)) and 90% confidence interval for GSK2285403 were calculated.
- non Inferiority Comment
- AUC(0-inf) of GSK2285403 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
- non Inferiority Type
- NON_INFERIORITY_OR_EQUIVALENCE
- param Type
- Geometric Mean Ratio
- param Value
- 0.92
- ci Lower Limit
- 0.81
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 1.29
- estimate Comment
- Geometric mean ratio (Day 15 AUC(0-t)/ Day 1 AUC(0-t)) and 90% confidence interval for GSK2298683 were calculated.
- non Inferiority Comment
- AUC(0-t) of GSK2298683 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
- non Inferiority Type
- NON_INFERIORITY_OR_EQUIVALENCE
- param Type
- Geometric Mean Ratio
- param Value
- 1.02
- ci Lower Limit
- 0.76
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 1.37
- estimate Comment
- Geometric mean ratio (Day 15 AUC(0-t)/ Day 1 AUC(0-t)) and 90% confidence interval for GSK2167542 were calculated.
- non Inferiority Comment
- AUC(0-t) of GSK2167542 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
- non Inferiority Type
- NON_INFERIORITY_OR_EQUIVALENCE
- param Type
- Geometric Mean Ratio
- param Value
- 1.02
- classes
- categories
- measurements
- group Id
- OG000
- lower Limit
- 2205
- upper Limit
- 3390
- value
- 2734
- group Id
- OG001
- lower Limit
- 2219
- upper Limit
- 3411
- value
- 2751
- denoms
- counts
- group Id
- OG000
- value
- 8
- group Id
- OG001
- value
- 8
- units
- Participants
- title
- GSK2118436 AUC (0-t)
- categories
- measurements
- group Id
- OG000
- lower Limit
- 2578
- upper Limit
- 3797
- value
- 3128
- group Id
- OG001
- lower Limit
- 2445
- upper Limit
- 3556
- value
- 2949
- denoms
- counts
- group Id
- OG000
- value
- 8
- group Id
- OG001
- value
- 8
- units
- Participants
- title
- GSK2118436 AUC (0-inf)
- categories
- measurements
- group Id
- OG000
- lower Limit
- 1684
- upper Limit
- 2959
- value
- 2232
- group Id
- OG001
- lower Limit
- 1899
- upper Limit
- 2753
- value
- 2287
- denoms
- counts
- group Id
- OG000
- value
- 8
- group Id
- OG001
- value
- 8
- units
- Participants
- title
- GSK2285403 AUC (0-t)
- categories
- measurements
- group Id
- OG000
- lower Limit
- 2231
- upper Limit
- 3562
- value
- 2819
- group Id
- OG001
- lower Limit
- 2097
- upper Limit
- 2974
- value
- 2497
- denoms
- counts
- group Id
- OG000
- value
- 8
- group Id
- OG001
- value
- 8
- units
- Participants
- title
- GSK2285403 AUC (0-inf)
- categories
- measurements
- group Id
- OG000
- lower Limit
- 10347
- upper Limit
- 15738
- value
- 12761
- group Id
- OG001
- lower Limit
- 10475
- upper Limit
- 16266
- value
- 13053
- denoms
- counts
- group Id
- OG000
- value
- 8
- group Id
- OG001
- value
- 8
- units
- Participants
- title
- GSK2298683 AUC (0-t)
- denoms
- counts
- group Id
- OG000
- value
- 0
- group Id
- OG001
- value
- 0
- units
- Participants
- title
- GSK2298683 AUC (0-inf)
- categories
- measurements
- group Id
- OG000
- lower Limit
- 188
- upper Limit
- 390
- value
- 270
- group Id
- OG001
- lower Limit
- 230
- upper Limit
- 332
- value
- 276
- denoms
- counts
- group Id
- OG000
- value
- 8
- group Id
- OG001
- value
- 8
- units
- Participants
- title
- GSK2167542 AUC (0-t)
- denoms
- counts
- group Id
- OG000
- value
- 0
- group Id
- OG001
- value
- 0
- units
- Participants
- title
- GSK2167542 AUC (0-inf)
- denoms
- counts
- group Id
- OG000
- value
- 8
- group Id
- OG001
- value
- 8
- units
- Participants
- description
- Blood samples for PK analysis of dabrafenib and its metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were obtained at pre-dose and at 1, 2, 3, 4, 6, 8, 10, and 24 hours after dabrafenib administration. AUC is defined as the area under the dabrafenib concentration-time curve as a measure of drug exposure. AUC (0-inf) is defined as the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time. AUC (0-t) is defined as area under the concentration-time curve from time zero (pre-dose) to the last time of quantifiable concentration. Date are reported as geometric least square means.
- dispersion Type
- 95% Confidence Interval
- groups
- description
- Participants received a single dose of dabrafenib 75 mg gelatin capsules alone on Day 1.
- id
- OG000
- title
- Part A: Dabrafenib 75 mg
- description
- Participants received a single dose of dabrafenib 75 mg gelatin capsules with repeat dose trametinib (Day 15).
- id
- OG001
- title
- Part A: Dabrafenib 75 mg + Trametinib 2 mg
- param Type
- GEOMETRIC_MEAN
- population Description
- PK Population
- reporting Status
- POSTED
- time Frame
- Day 15
- title
- Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites
- type
- PRIMARY
- unit Of Measure
- ng*hour/mL (ng*hr/mL)
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Preserved source evidence · Independent clinical review pending · Not medical advice
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