NCT04579679 · OUTCOME
Cohort D: Geometric Least Squares (LS) Mean Ratio of Cytochrome P450 (CYP3A4), P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) Substrates at Cycle 1 Day 15 to Baseline
Open-Label Surufatinib in European Patients With NET · Source last updated 2025-07-25
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- NUMBER
- Unit
- Ratio of geometric LS mean
- Interval / dispersion
- 90% Confidence Interval
- Time frame
- Baseline (Day -2) and Cycle 1 Day 15
What was measured
Participants were administered midazolam, fexofenadine and rosuvastatin (as part of the drug cocktail) as a single dose on Day -2 (without surufatinib) and on Cycle 1 Day 15 (with surufatinib). Separate blood samples were collected for measurement of plasma concentrations of each probe substrate and surufatinib. Probe substrate of midazolam was CYP3A4, fexofenadine was P-gp and rosuvastatin was BCRP. Ratio of LS Mean for maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) and area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) are presented as Cycle 1 Day 15/Day -2.
Analysis population: The PK evaluable population included all patients who received at least 1 dose of the study drug and had sufficient concentration data to derive at least 1 PK parameter.
Groups in this outcome
Cohort D (NET, Any)
Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
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 |
|---|
| Cohort D (NET, Any) | 6 |
|---|
Reported measurements
Midazolam (CYP3A4 substrate), Cmax
Values in Ratio of geometric LS mean · Interval/dispersion: 90% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Cohort D (NET, Any) | 1.69 | Not reported | 1.20 | 2.39 | Not reported |
|---|
Midazolam (CYP3A4 substrate), AUC0-t
Values in Ratio of geometric LS mean · Interval/dispersion: 90% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Cohort D (NET, Any) | 1.70 | Not reported | 1.14 | 2.52 | Not reported |
|---|
Midazolam (CYP3A4 substrate), AUC0-inf
Values in Ratio of geometric LS mean · Interval/dispersion: 90% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Cohort D (NET, Any) | 1.71 | Not reported | 1.16 | 2.53 | Not reported |
|---|
Fexofenadine (P-gp substrate), Cmax
Values in Ratio of geometric LS mean · Interval/dispersion: 90% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Cohort D (NET, Any) | 2.03 | Not reported | 1.51 | 2.75 | Not reported |
|---|
Fexofenadine (P-gp substrate), AUC0-t
Values in Ratio of geometric LS mean · Interval/dispersion: 90% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Cohort D (NET, Any) | 2.12 | Not reported | 1.65 | 2.73 | Not reported |
|---|
Fexofenadine (P-gp substrate), AUC0-inf
Values in Ratio of geometric LS mean · Interval/dispersion: 90% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Cohort D (NET, Any) | 2.14 | Not reported | 1.64 | 2.78 | Not reported |
|---|
Rosuvastatin (BCRP substrate), Cmax
Values in Ratio of geometric LS mean · Interval/dispersion: 90% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Cohort D (NET, Any) | 2.23 | Not reported | 1.59 | 3.14 | Not reported |
|---|
Rosuvastatin (BCRP substrate), AUC0-t
Values in Ratio of geometric LS mean · Interval/dispersion: 90% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Cohort D (NET, Any) | 2.13 | Not reported | 1.31 | 3.48 | Not reported |
|---|
Rosuvastatin (BCRP substrate), AUC0-inf
Values in Ratio of geometric LS mean · Interval/dispersion: 90% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Cohort D (NET, Any) | 2.23 | Not reported | 1.23 | 4.01 | Not reported |
|---|
Complete source fields
- classes
- categories
- measurements
- group Id
- OG000
- lower Limit
- 1.20
- upper Limit
- 2.39
- value
- 1.69
- title
- Midazolam (CYP3A4 substrate), Cmax
- categories
- measurements
- group Id
- OG000
- lower Limit
- 1.14
- upper Limit
- 2.52
- value
- 1.70
- title
- Midazolam (CYP3A4 substrate), AUC0-t
- categories
- measurements
- group Id
- OG000
- lower Limit
- 1.16
- upper Limit
- 2.53
- value
- 1.71
- title
- Midazolam (CYP3A4 substrate), AUC0-inf
- categories
- measurements
- group Id
- OG000
- lower Limit
- 1.51
- upper Limit
- 2.75
- value
- 2.03
- title
- Fexofenadine (P-gp substrate), Cmax
- categories
- measurements
- group Id
- OG000
- lower Limit
- 1.65
- upper Limit
- 2.73
- value
- 2.12
- title
- Fexofenadine (P-gp substrate), AUC0-t
- categories
- measurements
- group Id
- OG000
- lower Limit
- 1.64
- upper Limit
- 2.78
- value
- 2.14
- title
- Fexofenadine (P-gp substrate), AUC0-inf
- categories
- measurements
- group Id
- OG000
- lower Limit
- 1.59
- upper Limit
- 3.14
- value
- 2.23
- title
- Rosuvastatin (BCRP substrate), Cmax
- categories
- measurements
- group Id
- OG000
- lower Limit
- 1.31
- upper Limit
- 3.48
- value
- 2.13
- title
- Rosuvastatin (BCRP substrate), AUC0-t
- categories
- measurements
- group Id
- OG000
- lower Limit
- 1.23
- upper Limit
- 4.01
- value
- 2.23
- title
- Rosuvastatin (BCRP substrate), AUC0-inf
- description
- Participants were administered midazolam, fexofenadine and rosuvastatin (as part of the drug cocktail) as a single dose on Day -2 (without surufatinib) and on Cycle 1 Day 15 (with surufatinib). Separate blood samples were collected for measurement of plasma concentrations of each probe substrate and surufatinib. Probe substrate of midazolam was CYP3A4, fexofenadine was P-gp and rosuvastatin was BCRP. Ratio of LS Mean for maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) and area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) are presented as Cycle 1 Day 15/Day -2.
- dispersion Type
- 90% Confidence Interval
- groups
- description
- Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
- id
- OG000
- title
- Cohort D (NET, Any)
- param Type
- NUMBER
- population Description
- The PK evaluable population included all patients who received at least 1 dose of the study drug and had sufficient concentration data to derive at least 1 PK parameter.
- reporting Status
- POSTED
- time Frame
- Baseline (Day -2) and Cycle 1 Day 15
- title
- Cohort D: Geometric Least Squares (LS) Mean Ratio of Cytochrome P450 (CYP3A4), P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) Substrates at Cycle 1 Day 15 to Baseline
- type
- SECONDARY
- unit Of Measure
- Ratio of geometric LS mean
Download exact source JSON → · Snapshot ctgov-results-25a395029948b04d52b1253f
Preserved source evidence · Not medical advice
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