Healthy Volunteers
Conditions
Brief summary
The purpose of the study is to investigate how the test drug, PBT2, is taken up, broken down and removed from the body when given as an oral capsule, a radiolabelled oral suspension and a radiolabelled intravenous injection.
Interventions
DRUGIV PBT2 microtracer and oral PBT2 single dose
DRUGoral 14C-PBT2
Sponsors
Prana Biotechnology Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
30 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males * Body mass index of 18.0 to 35.0 kg/m2
Exclusion criteria
* History of any drug or alcohol abuse in the past 2 years * Regular alcohol consumption \>21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) * Current smokers and those who have smoked within the last 12 months * Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. * Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator * Positive drugs of abuse test result * Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results * History of cardiovascular, renal, hepatic, chronic respiratory or GI disease as judged by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Bioavailability of PBT2 (F%) | 0 to 72 hours post oral dose | Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose, computed as AUC(oral)/AUC(IV), with range from 0% (no drug) to 100% (all of the administered drug). |
| Mass Balance | 168 h (7 days) post dose | Amount excreted as a percentage of the administered dose (%Ae) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of PBT2 | 72 h post oral dose | As assessed by the number of participants with adverse events |
| IV PK Profile of [14C]-PBT2 and Total Radioactivity as Assessed by AUC(0 Last) | 0 to 72 h post oral dose | Area under the plasma concentration vs time curve from time 0h to the last time point of IV \[14C\]-PBT2 . |
| Oral PK Profile of [14C]-PBT2 as Assessed by AUC(0-last) | 0 to 72 hours | area under the plasma concentration vs time curve to the last timepoint |
| Ratio of Whole Blood, Plasma [14C] PBT2 at 24 Hours | 0 to 24 hours | Ratio of whole blood, plasma \[14C\] PBT2 at 24 hours |
| Oral PK Profile of PBT2 as Assessed by AUC(0-last) | 72 h post oral dose | Area under the plasma concentration vs time curve from time 0h to the last time point of oral PBT2 . |
Countries
United Kingdom
Participant flow
Recruitment details
Participants were screened and enrolled into one study site in the United Kingdom.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants In Part One (Absolute Bioavailability), a single dose of oral PBT2 250 mg capsule administered followed by IV PBT2 microtracer. Following completion of Part One, participants crossed over into Part Two (Radiolabelled AME), where a single dose of oral PBT2 250 mg 14C suspension was administered. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 51.8 years STANDARD_DEVIATION 5.9 |
| BMI | 27.55 kg/m^2 STANDARD_DEVIATION 4.72 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United Kingdom | 6 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Absolute Bioavailability of PBT2 (F%)
Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose, computed as AUC(oral)/AUC(IV), with range from 0% (no drug) to 100% (all of the administered drug).
Time frame: 0 to 72 hours post oral dose
Population: PK Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part One Absolute Bioavailability | Absolute Bioavailability of PBT2 (F%) | 15.936 percentage of absolute bioavailability | Standard Deviation 28.2 |
Primary
Mass Balance
Amount excreted as a percentage of the administered dose (%Ae)
Time frame: 168 h (7 days) post dose
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part One Absolute Bioavailability | Mass Balance | 98.65 percentage of administered dose | Standard Deviation 1.28 |
Secondary
IV PK Profile of [14C]-PBT2 and Total Radioactivity as Assessed by AUC(0 Last)
Area under the plasma concentration vs time curve from time 0h to the last time point of IV \[14C\]-PBT2 .
Time frame: 0 to 72 h post oral dose
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part One Absolute Bioavailability | IV PK Profile of [14C]-PBT2 and Total Radioactivity as Assessed by AUC(0 Last) | 3.40 ng*hr/ml | Geometric Coefficient of Variation 28.8 |
Secondary
Oral PK Profile of [14C]-PBT2 as Assessed by AUC(0-last)
area under the plasma concentration vs time curve to the last timepoint
Time frame: 0 to 72 hours
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part One Absolute Bioavailability | Oral PK Profile of [14C]-PBT2 as Assessed by AUC(0-last) | 1660 ng*hr/mL | Geometric Coefficient of Variation 48.3 |
Secondary
Oral PK Profile of PBT2 as Assessed by AUC(0-last)
Area under the plasma concentration vs time curve from time 0h to the last time point of oral PBT2 .
Time frame: 72 h post oral dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part One Absolute Bioavailability | Oral PK Profile of PBT2 as Assessed by AUC(0-last) | 1330 ng*hr/ml | Geometric Coefficient of Variation 51.2 |
Secondary
Ratio of Whole Blood, Plasma [14C] PBT2 at 24 Hours
Ratio of whole blood, plasma \[14C\] PBT2 at 24 hours
Time frame: 0 to 24 hours
Population: PK population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part One Absolute Bioavailability | Ratio of Whole Blood, Plasma [14C] PBT2 at 24 Hours | 0.488 ratio [14C] PBT2 | Geometric Coefficient of Variation 5.1 |
Secondary
Safety and Tolerability of PBT2
As assessed by the number of participants with adverse events
Time frame: 72 h post oral dose
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part One Absolute Bioavailability | Safety and Tolerability of PBT2 | 1 participants |