Healthy
Conditions
Keywords
HSV, HIV, Herpes, volunteers, drug-drug interaction
Brief summary
ASP2151 is an experimental treatment for herpes. HIV infected people are susceptible to contracting other infections because of their compromised immune system. As HIV patients will be taking drugs to treat the virus this study aims to see if ASP2151 would interact with one of the drugs that is commonly prescribed to HIV patients (ritonavir).
Interventions
DRUGASP2151
DRUGritonavir
Sponsors
Maruho Europe Limited
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers * Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial. * Willingness to give written consent to participate after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate.
Exclusion criteria
* Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer. * Any of the following liver function tests higher than 1.5 times the ULN at the screening visit: aspartate aminotransferase (AST), alanine aminotransferase (ALT), ALP, bilirubin, gamma glutamyl transpeptidase (gamma-GT). * Platelet counts outside normal limits. * Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the trial or make it unnecessarily hazardous. * Clinically significant impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness. * History of bleeding diathesis. * Surgery (eg stomach bypass) or medical condition that might affect absorption of medicines. * Presence or history of severe adverse reaction to any drug, history of multiple drug allergies (multiple defined as \>3), or sensitivity to trial medication. * Use, during the 28 days before the first dose of trial medication, of any prescription medicine, or any other medicine or herbal remedy (such as St John's wort) known to interfere with the CYP3A4 metabolic pathway (unless judged as not clinical significant by the investigator and sponsor). * Use, during the 7 days before the first dose of trial medication, of any over-the-counter medicine, with the exception of paracetamol (acetaminophen). * Participation in another clinical trial of a new chemical entity or a prescription medicine within the previous 3 months. * Loss of more than 400 mL blood during the 3 months before the trial, eg as a blood donor. * Presence or history of drug or alcohol abuse, or intake of more than 21 units of alcohol weekly or more than 10 cigarettes daily. * Evidence of drug abuse on urine testing. * Positive test for hepatitis B, hepatitis C, HIV1 or HIV2. * Blood pressure (BP) and heart rate (HR) in seated position at the screening examination outside the ranges 90-140 mm Hg systolic, 40-90 mm Hg diastolic; heart rate 40\_100 beats/min.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Peak Plasma Concentration (Cmax) of ASP2151 | Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention |
| Apparent Volume of Distribution (Vd/F) of ASP2151 | Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention |
| Apparent Total Body Clearance (CL/F) of ASP2151 From Plasma | Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention |
| Half-Life (t1/2) of ASP2151 | Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention |
| Area Under the Curve (AUC) of ASP2151 | Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention |
| Time of Peak Concentration (Tmax) of ASP2151 | Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious and Non-Serious Adverse Events | Up to 31 days | Refer to the result of adverse event. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration (Cmax) of ASP1955888-00 | Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention | ASP1955888-00 is a metabolite of the study drug (ASP2151) |
| Apparent Volume of Distribution (Vd/F) of ASP1955888-00 | Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention | ASP1955888-00 is a metabolite of the study drug (ASP2151) |
| Apparent Total Body Clearance (CL/F) From Plasma of ASP1955888-00 | Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention | ASP1955888-00 is a metabolite of the study drug (ASP2151) |
| Half-life (t1/2) of ASP1955888-00 | Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention | ASP1955888-00 is a metabolite of the study drug (ASP2151) |
| Area Under the Curve (AUC) of ASP1955888-00 | Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention | ASP1955888-00 is a metabolite of the study drug (ASP2151) |
| Time of Peak Concentration (Tmax) of ASP1955888-00 | Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention | ASP1955888-00 is a metabolite of the study drug (ASP2151) |
Countries
United Kingdom
Participant flow
Recruitment details
Participants took part in the study at one investigative site in United Kingdom from 05-September 2014 to 04-December 2014
Participants by arm
| Arm | Count |
|---|---|
| 400mg ASP2151 ASP2151 400mg alone followed by ASP2151 400mg + 600 mg ritonavir, or vice versa. | 24 |
| 1200mg ASP2151 ASP2151 1200mg alone followed by ASP2151 1200mg + 600 mg ritonavir, or vice versa. | 24 |
| Total | 48 |
Baseline characteristics
| Characteristic | 400mg ASP2151 | 1200mg ASP2151 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 23 Participants | 47 Participants |
| Age, Continuous | 28.2 year STANDARD_DEVIATION 6.4 | 27 year STANDARD_DEVIATION 4.9 | 27.6 year STANDARD_DEVIATION 5.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 24 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 15 Participants | 32 Participants |
| Region of Enrollment United Kingdom | 24 Participants | 24 Participants | 48 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 24 Participants | 24 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 8 / 24 | 17 / 24 | 15 / 24 | 13 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Apparent Total Body Clearance (CL/F) of ASP2151 From Plasma
Time frame: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 400 mg ASP2151 Alone | Apparent Total Body Clearance (CL/F) of ASP2151 From Plasma | 18.314 L/h | Standard Deviation 7.2654 |
| 400mg ASP2151 With Ritonavir | Apparent Total Body Clearance (CL/F) of ASP2151 From Plasma | 6.815 L/h | Standard Deviation 1.6607 |
| 1200 mg ASP2151 Alone | Apparent Total Body Clearance (CL/F) of ASP2151 From Plasma | 25.735 L/h | Standard Deviation 7.5753 |
| 1200mg ASP2151 With Ritonavir | Apparent Total Body Clearance (CL/F) of ASP2151 From Plasma | 7.63 L/h | Standard Deviation 1.9843 |
Primary
Apparent Volume of Distribution (Vd/F) of ASP2151
Time frame: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 400 mg ASP2151 Alone | Apparent Volume of Distribution (Vd/F) of ASP2151 | 190.1 L | Standard Deviation 56.912 |
| 400mg ASP2151 With Ritonavir | Apparent Volume of Distribution (Vd/F) of ASP2151 | 123.17 L | Standard Deviation 28.366 |
| 1200 mg ASP2151 Alone | Apparent Volume of Distribution (Vd/F) of ASP2151 | 266.33 L | Standard Deviation 79.948 |
| 1200mg ASP2151 With Ritonavir | Apparent Volume of Distribution (Vd/F) of ASP2151 | 139.33 L | Standard Deviation 43.231 |
Primary
Area Under the Curve (AUC) of ASP2151
Time frame: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 400 mg ASP2151 Alone | Area Under the Curve (AUC) of ASP2151 | 23162.4 h*ng/mL | Geometric Coefficient of Variation 34.2 |
| 400mg ASP2151 With Ritonavir | Area Under the Curve (AUC) of ASP2151 | 60225.3 h*ng/mL | Geometric Coefficient of Variation 23 |
| 1200 mg ASP2151 Alone | Area Under the Curve (AUC) of ASP2151 | 48532.3 h*ng/mL | Geometric Coefficient of Variation 29.3 |
| 1200mg ASP2151 With Ritonavir | Area Under the Curve (AUC) of ASP2151 | 162131.6 h*ng/mL | Geometric Coefficient of Variation 25.3 |
Primary
Half-Life (t1/2) of ASP2151
Time frame: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 400 mg ASP2151 Alone | Half-Life (t1/2) of ASP2151 | 7.375 h | Geometric Coefficient of Variation 14.9 |
| 400mg ASP2151 With Ritonavir | Half-Life (t1/2) of ASP2151 | 12.575 h | Geometric Coefficient of Variation 15.9 |
| 1200 mg ASP2151 Alone | Half-Life (t1/2) of ASP2151 | 7.178 h | Geometric Coefficient of Variation 17.5 |
| 1200mg ASP2151 With Ritonavir | Half-Life (t1/2) of ASP2151 | 12.498 h | Geometric Coefficient of Variation 19.6 |
Primary
Peak Plasma Concentration (Cmax) of ASP2151
Time frame: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 400 mg ASP2151 Alone | Peak Plasma Concentration (Cmax) of ASP2151 | 1845.7 ng/mL | Geometric Coefficient of Variation 25.4 |
| 400mg ASP2151 With Ritonavir | Peak Plasma Concentration (Cmax) of ASP2151 | 2518.7 ng/mL | Geometric Coefficient of Variation 21.9 |
| 1200 mg ASP2151 Alone | Peak Plasma Concentration (Cmax) of ASP2151 | 3804 ng/mL | Geometric Coefficient of Variation 28.8 |
| 1200mg ASP2151 With Ritonavir | Peak Plasma Concentration (Cmax) of ASP2151 | 6211.6 ng/mL | Geometric Coefficient of Variation 29.2 |
Primary
Time of Peak Concentration (Tmax) of ASP2151
Time frame: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 400 mg ASP2151 Alone | Time of Peak Concentration (Tmax) of ASP2151 | 3 h |
| 400mg ASP2151 With Ritonavir | Time of Peak Concentration (Tmax) of ASP2151 | 4 h |
| 1200 mg ASP2151 Alone | Time of Peak Concentration (Tmax) of ASP2151 | 3.025 h |
| 1200mg ASP2151 With Ritonavir | Time of Peak Concentration (Tmax) of ASP2151 | 4 h |
Secondary
Number of Participants With Serious and Non-Serious Adverse Events
Refer to the result of adverse event.
Time frame: Up to 31 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 400 mg ASP2151 Alone | Number of Participants With Serious and Non-Serious Adverse Events | Non-serious adverse event | 8 participants |
| 400 mg ASP2151 Alone | Number of Participants With Serious and Non-Serious Adverse Events | serious adverse event | 0 participants |
| 400mg ASP2151 With Ritonavir | Number of Participants With Serious and Non-Serious Adverse Events | serious adverse event | 0 participants |
| 400mg ASP2151 With Ritonavir | Number of Participants With Serious and Non-Serious Adverse Events | Non-serious adverse event | 17 participants |
| 1200 mg ASP2151 Alone | Number of Participants With Serious and Non-Serious Adverse Events | Non-serious adverse event | 15 participants |
| 1200 mg ASP2151 Alone | Number of Participants With Serious and Non-Serious Adverse Events | serious adverse event | 0 participants |
| 1200mg ASP2151 With Ritonavir | Number of Participants With Serious and Non-Serious Adverse Events | Non-serious adverse event | 13 participants |
| 1200mg ASP2151 With Ritonavir | Number of Participants With Serious and Non-Serious Adverse Events | serious adverse event | 0 participants |
Other Pre-specified
Apparent Total Body Clearance (CL/F) From Plasma of ASP1955888-00
ASP1955888-00 is a metabolite of the study drug (ASP2151)
Time frame: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 400 mg ASP2151 Alone | Apparent Total Body Clearance (CL/F) From Plasma of ASP1955888-00 | 156.72 L/h | Standard Deviation 43.197 |
| 400mg ASP2151 With Ritonavir | Apparent Total Body Clearance (CL/F) From Plasma of ASP1955888-00 | 540.93 L/h | Standard Deviation 68.554 |
| 1200 mg ASP2151 Alone | Apparent Total Body Clearance (CL/F) From Plasma of ASP1955888-00 | 207.45 L/h | Standard Deviation 59.311 |
| 1200mg ASP2151 With Ritonavir | Apparent Total Body Clearance (CL/F) From Plasma of ASP1955888-00 | 775.35 L/h | Standard Deviation 315.166 |
Other Pre-specified
Apparent Volume of Distribution (Vd/F) of ASP1955888-00
ASP1955888-00 is a metabolite of the study drug (ASP2151)
Time frame: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 400 mg ASP2151 Alone | Apparent Volume of Distribution (Vd/F) of ASP1955888-00 | 1840.8 L | Standard Deviation 559.49 |
| 400mg ASP2151 With Ritonavir | Apparent Volume of Distribution (Vd/F) of ASP1955888-00 | 21474 L | Standard Deviation 4135.72 |
| 1200 mg ASP2151 Alone | Apparent Volume of Distribution (Vd/F) of ASP1955888-00 | 2340.7 L | Standard Deviation 877.14 |
| 1200mg ASP2151 With Ritonavir | Apparent Volume of Distribution (Vd/F) of ASP1955888-00 | 27624.2 L | Standard Deviation 14413.73 |
Other Pre-specified
Area Under the Curve (AUC) of ASP1955888-00
ASP1955888-00 is a metabolite of the study drug (ASP2151)
Time frame: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 400 mg ASP2151 Alone | Area Under the Curve (AUC) of ASP1955888-00 | 2636.2 h*ng/mL | Geometric Coefficient of Variation 25.8 |
| 400mg ASP2151 With Ritonavir | Area Under the Curve (AUC) of ASP1955888-00 | 744.4 h*ng/mL | Geometric Coefficient of Variation 12 |
| 1200 mg ASP2151 Alone | Area Under the Curve (AUC) of ASP1955888-00 | 6023.1 h*ng/mL | Geometric Coefficient of Variation 30.2 |
| 1200mg ASP2151 With Ritonavir | Area Under the Curve (AUC) of ASP1955888-00 | 1646.1 h*ng/mL | Geometric Coefficient of Variation 37.3 |
Other Pre-specified
Half-life (t1/2) of ASP1955888-00
ASP1955888-00 is a metabolite of the study drug (ASP2151)
Time frame: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 400 mg ASP2151 Alone | Half-life (t1/2) of ASP1955888-00 | 8.063 h | Geometric Coefficient of Variation 18.1 |
| 400mg ASP2151 With Ritonavir | Half-life (t1/2) of ASP1955888-00 | 40.213 h | Geometric Coefficient of Variation 56.6 |
| 1200 mg ASP2151 Alone | Half-life (t1/2) of ASP1955888-00 | 7.617 h | Geometric Coefficient of Variation 18.6 |
| 1200mg ASP2151 With Ritonavir | Half-life (t1/2) of ASP1955888-00 | 42.197 h | Geometric Coefficient of Variation 69.1 |
Other Pre-specified
Peak Plasma Concentration (Cmax) of ASP1955888-00
ASP1955888-00 is a metabolite of the study drug (ASP2151)
Time frame: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 400 mg ASP2151 Alone | Peak Plasma Concentration (Cmax) of ASP1955888-00 | 189.9 ng/mL | Geometric Coefficient of Variation 27.7 |
| 400mg ASP2151 With Ritonavir | Peak Plasma Concentration (Cmax) of ASP1955888-00 | 21.6 ng/mL | Geometric Coefficient of Variation 70.7 |
| 1200 mg ASP2151 Alone | Peak Plasma Concentration (Cmax) of ASP1955888-00 | 421.5 ng/mL | Geometric Coefficient of Variation 36.7 |
| 1200mg ASP2151 With Ritonavir | Peak Plasma Concentration (Cmax) of ASP1955888-00 | 56.2 ng/mL | Geometric Coefficient of Variation 79.9 |
Other Pre-specified
Time of Peak Concentration (Tmax) of ASP1955888-00
ASP1955888-00 is a metabolite of the study drug (ASP2151)
Time frame: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 400 mg ASP2151 Alone | Time of Peak Concentration (Tmax) of ASP1955888-00 | 3 h |
| 400mg ASP2151 With Ritonavir | Time of Peak Concentration (Tmax) of ASP1955888-00 | 1.5 h |
| 1200 mg ASP2151 Alone | Time of Peak Concentration (Tmax) of ASP1955888-00 | 3 h |
| 1200mg ASP2151 With Ritonavir | Time of Peak Concentration (Tmax) of ASP1955888-00 | 1.01 h |