Hypertension
Conditions
Keywords
Fimasartan
Brief summary
The purpose of this study is to evaluate the pharmacokinetics and safety of Fimasartan and rosuvastatin when coadministered or administered alone as a single dose or as multiple doses to healthy male subjects.
Detailed description
This is an open-label, randomized, 6-sequence, 3-period, 3-way crossover study. Within each period, randomized subjects will be 2 dosing regimens with the same drug(fimasartan or rosuvastatin) or study drug combination(fimasartan+rosuvastatin) on day 1 and quaque die(qd) from day 4 to day 10. After day 1 and day 10 dosing will be followed by pharmacokinetic sampling for 48 hours or 72 hours.
Interventions
DRUGFimasartan
DRUGRosuvastatin
DRUGFimasartan + Rosuvastatin
Sponsors
Boryung Pharmaceutical Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Caucasian male 19-55 years of age. 2. Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at screening. 3. Medically healthy with no clinically significant medical history. 4. Understands the study procedures in the Informed consent form (ICF), and be willing and able to comply with the protocol.
Exclusion criteria
1. History or presence of clinically significant medical or psychiatric condition or disease. 2. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV). 3. Seated blood pressure is less than 90/60 mmHg or greater than 140/90 mmHg at screening. 4. Plasma donation within 7 days prior to the first dose of study drug. 5. Participation in another clinical trial within 28 days prior to the first dose of study drug(s).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve | For Fimasartan PK(Treatment A and C) : Post-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 in each period/For Rosuvastatin PK(Treatment B and C) : Post-dose, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 in each period | This Outcome is the Area Calculated using the Linear Trapezoidal with Linear Interpolation Method |
| Maximum Observed Concentration | For Fimasartan PK(Treatment A and C) : Post-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 in each period/For Rosuvastatin PK(Treatment B and C) : Post-dose, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 in each period | This Outcome is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated. |
| Time to Reach Maximum Observed Plasma Concentration | For Fimasartan PK(Treatment A and C) : Post-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 in each period/For Rosuvastatin PK(Treatment B and C) : Post-dose, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 in each period | This Outcome is the time it takes a drug to reach Cmax |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence 2 (ACB) Period 1(Treatment A) → Period 2(Treatment C) → Period 3(Treatment B)
There will be a washout of at least 7 days between the each period.
Fimasartan
Rosuvastatin
Fimasartan + Rosuvastatin | 6 |
| Sequence 3 (BAC) Period 1(Treatment A) → Period 2(Treatment B) → Period 3(Treatment 3)
There will be a washout of at least 7 days between the each period.
Fimasartan
Rosuvastatin
Fimasartan + Rosuvastatin | 6 |
| Sequence 1 (ABC) Period 1(Treatment A) → Period 2(Treatment B) → Period 3(Treatment C)
There will be a washout of at least 7 days between the each period.
Fimasartan
Rosuvastatin
Fimasartan + Rosuvastatin | 6 |
| Sequence 4 (BCA) Period 1(Treatment B) → Period 2(Treatment C) → Period 3(Treatment A)
There will be a washout of at least 7 days between the each period.
Fimasartan
Rosuvastatin
Fimasartan + Rosuvastatin | 6 |
| Sequence 5 (CAB) Period 1(Treatment C) → Period 2(Treatment A) → Period 3(Treatment B)
There will be a washout of at least 7 days between the each period.
Fimasartan
Rosuvastatin
Fimasartan + Rosuvastatin | 6 |
| Sequence 6 (CBA) Period 1(Treatment C) → Period 2(Treatment B) → Period 3(Treatment A)
There will be a washout of at least 7 days between the each period.
Fimasartan
Rosuvastatin
Fimasartan + Rosuvastatin | 6 |
| Total | 36 |
Baseline characteristics
| Characteristic | Sequence 2 (ACB) | Sequence 3 (BAC) | Sequence 1 (ABC) | Sequence 4 (BCA) | Sequence 5 (CAB) | Sequence 6 (CBA) | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 36 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 36 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 33 | 0 / 35 | 0 / 34 | 0 / 34 | 0 / 34 |
| other Total, other adverse events | 2 / 34 | 6 / 33 | 6 / 35 | 7 / 34 | 6 / 34 | 8 / 34 |
| serious Total, serious adverse events | 0 / 34 | 0 / 33 | 0 / 35 | 1 / 34 | 0 / 34 | 0 / 34 |
Outcome results
Primary
Area Under the Concentration-time Curve
This Outcome is the Area Calculated using the Linear Trapezoidal with Linear Interpolation Method
Time frame: For Fimasartan PK(Treatment A and C) : Post-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 in each period/For Rosuvastatin PK(Treatment B and C) : Post-dose, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 in each period
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A(Single Dose) | Area Under the Concentration-time Curve | 690.43 ng*hr/mL |
| Treatment A(Multiple Dose) | Area Under the Concentration-time Curve | 820.86 ng*hr/mL |
| Treatment B(Single Dose) | Area Under the Concentration-time Curve | 86.442 ng*hr/mL |
| Treatment B(Multiple Dose) | Area Under the Concentration-time Curve | 114.55 ng*hr/mL |
| Treatment C(Single Dose_Fimasartan) | Area Under the Concentration-time Curve | 702.20 ng*hr/mL |
| Treatment C(Single Dose_Rosuvastatin) | Area Under the Concentration-time Curve | 85.078 ng*hr/mL |
| Treatment C(Multiple Dose_Fimasartan) | Area Under the Concentration-time Curve | 880.19 ng*hr/mL |
| Treatment C(Multiple Dose_Rosuvastatin) | Area Under the Concentration-time Curve | 98.957 ng*hr/mL |
Primary
Maximum Observed Concentration
This Outcome is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated.
Time frame: For Fimasartan PK(Treatment A and C) : Post-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 in each period/For Rosuvastatin PK(Treatment B and C) : Post-dose, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 in each period
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A(Single Dose) | Maximum Observed Concentration | 289.12 ng/mL |
| Treatment A(Multiple Dose) | Maximum Observed Concentration | 362.14 ng/mL |
| Treatment B(Single Dose) | Maximum Observed Concentration | 9.305 ng/mL |
| Treatment B(Multiple Dose) | Maximum Observed Concentration | 11.706 ng/mL |
| Treatment C(Single Dose_Fimasartan) | Maximum Observed Concentration | 283.73 ng/mL |
| Treatment C(Single Dose_Rosuvastatin) | Maximum Observed Concentration | 341.92 ng/mL |
| Treatment C(Multiple Dose_Fimasartan) | Maximum Observed Concentration | 12.581 ng/mL |
| Treatment C(Multiple Dose_Rosuvastatin) | Maximum Observed Concentration | 13.687 ng/mL |
Primary
Time to Reach Maximum Observed Plasma Concentration
This Outcome is the time it takes a drug to reach Cmax
Time frame: For Fimasartan PK(Treatment A and C) : Post-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 in each period/For Rosuvastatin PK(Treatment B and C) : Post-dose, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 in each period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A(Single Dose) | Time to Reach Maximum Observed Plasma Concentration | 0.749 hr |
| Treatment A(Multiple Dose) | Time to Reach Maximum Observed Plasma Concentration | 0.635 hr |
| Treatment B(Single Dose) | Time to Reach Maximum Observed Plasma Concentration | 2.999 hr |
| Treatment B(Multiple Dose) | Time to Reach Maximum Observed Plasma Concentration | 4.505 hr |
| Treatment C(Single Dose_Fimasartan) | Time to Reach Maximum Observed Plasma Concentration | 0.750 hr |
| Treatment C(Single Dose_Rosuvastatin) | Time to Reach Maximum Observed Plasma Concentration | 0.751 hr |
| Treatment C(Multiple Dose_Fimasartan) | Time to Reach Maximum Observed Plasma Concentration | 2.003 hr |
| Treatment C(Multiple Dose_Rosuvastatin) | Time to Reach Maximum Observed Plasma Concentration | 1.506 hr |