Healthy Adults
Conditions
Brief summary
To assess the safety of a single ascending dose of MEDI7836 in healthy adult male subjects and healthy adult female subjects of non-childbearing potential.
Detailed description
This is a Phase 1a, randomised, blinded (the investigator and subject will be blinded to treatment assignment and sponsor will be unblinded to treatment assignment), placebo-controlled study to evaluate the safety of single-ascending SC doses of MEDI7836 in healthy adult males subjects and healthy adult female subjects of non-childbearing potential. The study will be conducted at a single site in the United Kingdom (UK). Four dosing cohorts of MEDI7836 or placebo are planned for this study for a total of 32 subjects (24 subjects receiving MEDI7836, 8 subjects receiving placebo).
Interventions
DRUGPlacebo SC
Participants will receive a single-dose of Placebo subcutaneous (SC) injection on Day 1.
BIOLOGICALMEDI7836 Dose 1
Participants will receive a single-dose of MEDI7836 Dose 1 SC injection on Day 1.
BIOLOGICALMEDI7836 Dose 2
Participants will receive a single-dose of MEDI7836 Dose 2 SC injection on Day 1.
BIOLOGICALMEDI7836 Dose 3
Participants will receive a single-dose of MEDI7836 Dose 3 SC injection on Day 1.
BIOLOGICALMEDI7836 Dose 4
Participants will receive a single-dose of MEDI7836 Dose 4 SC injection on Day 1.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Vital signs, ECG, and laboratory parameters within normal range at screening and Day -1 2. Negative alcohol and drug screen at screening and Day -1 3. Able and willing to comply with the requirements of the protocol 4. Females subjects must have been surgically sterilised or be postmenopausal 5. Nonsterilised males who are sexually active with a female partner of childbearing potential or a female partner who has been surgically sterilised by bilateral tubal ligation must use a condom with spermicide with their partner from screening until the end of the study follow-up period
Exclusion criteria
1. Concurrent enrolment in another clinical study where the subject is receiving an investigational product 2. Individuals who are legally institutionalised 3. Receipt of any marketed or investigational biologic agent within 4 months 4. Receipt of any investigational non-biologic agent within 3 months or 5 half-lives prior to screening, whichever is longer 5. Use of any medication (prescription or over the counter, including herbal remedies) within 14 days or 5 half-lives of Day 1, 6. Known history of allergy or reaction to any component of the investigational product formulation 7. History of anaphylaxis following any biologic therapy 8. History of chronic alcohol or drug abuse within 12 months prior to screening, 9. Presence of a positive drug or alcohol screen at screening and Day -1. 10. Current smoker, or history of smoking within 6 months of screening 11. Pregnant or breastfeeding women 12. Any active medical or psychiatric condition or other reason which, in the opinion of the investigator or medical monitor, may compromise the safety of the subject in the study or interfere with evaluation of the investigational product or reduce the subject's ability to participate in the study 13. Any clinically relevant abnormal findings in physical examination, ECG, vital signs, haematology, clinical chemistry or urinalysis during screening or Day -1, 14. History of any known primary immunodeficiency disorder or use of immunosuppressive medication within 12 months of screening 15. History of a clinically significant infection requiring antibiotics or antiviral medication from 30 days prior to screening, up to and including Day 1 16. Diagnosis of a helminth parasitic infection within 6 months prior to screening that has not been treated with, or has failed to respond to, standard of care therapy 17. History of cancer, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy ≥ 12 months prior to screening or other malignancies treated with apparent success with curative therapy ≥ 5 years prior to screening 18. Positive tuberculosis (TB) test (Quantiferon-TB Gold) at screening or TB requiring treatment within the 12 months prior to the screening visit 19. Positive hepatitis B surface antigen, hepatitis B anti-core antibody, or hepatitis C virus antibody serology at screening. 20. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enter the study. 21. A positive human immunodeficiency virus test at screening or subject taking antiretroviral medications, as determined by medical history and/or subject's verbal report 22. Evidence of active liver disease, including jaundice or aspartate transaminase (AST), alanine transaminase (ALT), or alkaline phosphatase greater than twice the upper limit of normal (ULN) 23. Major surgery within 8 weeks prior to screening, or planed in-patient surgery or hospitalisation during the study period 24. Receipt of live attenuated vaccines 30 days prior to the date of screening Where participation in the study would result in donation of blood or blood products in excess of 500 mL within an 8-week period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | From Study Drug Administration to 281 Days Postdose | Any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received MEDI7836. Treatment-emergent adverse events between administration of investigational product and Day 281 that were absent before treatment or that worsened relative to pretreatment state. |
| Number of Participants With Injection Site Reactions | From Study Drug Administration to 281 Days Postdose | Participants were evaluated for manifestations of injection site reactions. |
| Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | From Study Drug Administration to 281 Days Postdose | An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Treatment-emergent adverse events between first dose of study drug and Day 281 after the last dose that were absent before treatment or that worsened relative to pre-treatment state. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed. |
| Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as Treatment-Emergent Adverse Events | From Study Drug Administration to 281 Days Postdose | Vital sign parameters included blood pressure, temperature, pulse rate, respiratory rate and weight. Physical examination included assessment of general appearance, weight, head, ears, eyes, nose, throat, neck, skin, cardiovascular system, respiratory system, abdominal system, and nervous system. Criteria for abnormal physical findings was based on investigator's discretion. TEAEs were present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug until Day 281 after the last dose of study drug. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | From Study Drug Administration to 281 Days Postdose | AEs observed in participants with clinically significant ECG abnormalities were assessed. ECG parameters included heart rate, RR, PR, QRS, QT and QTc intervals. Treatment-emergent adverse events between administration of investigational product and Day 281 that were absent before treatment or that worsened relative to pre-treatment state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI7836 | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | The Tmax is defined as actual sampling time to reach maximum observed MEDI7836 concentration. |
| Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) of MEDI7836 | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | Area under the concentration-time curve of the MEDI7836 in serum over the time interval from 0 extrapolated to infinity (AUC0-inf). |
| Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836 | Predose on Day 1 to 281 days Postdose | A participant was considered ADA-positive across the study if they had a positive reading at any time point during the study. |
| Apparent Terminal-Phase Volume of Distribution (Vz/F) of MEDI7836 | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | The apparent volume of distribution of MEDI7836 after a single dose, calculated according to the equation: Vz/F = Apparent total clearance (CL/F) / terminal phase rate constant (λz). |
| Area Under the Concentration-Time Curve From Zero to Last Observation (AUC [0-t]) of MEDI7836 | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | Area under the concentration-time curve of the MEDI7836 in serum over the time interval from 0 to the last quantifiable data point (AUC0-t). |
| Maximum Observed Serum Concentration (Cmax) of MEDI7836 | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | The Cmax is the maximum observed serum concentration of study drug. |
| Apparent Systemic Clearance (CL/F) of MEDI7836 | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Terminal Phase Elimination Half Life (T1/2) of MEDI7836 | Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose | Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum. |
Countries
United Kingdom
Participant flow
Pre-assignment details
A total of 79 participants were screened. Of these, 32 participants were randomized and treated in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single-dose of Placebo subcutaneous (SC) injection on Day 1. | 8 |
| MEDI7836 Dose 1 Participants received a single-dose of MEDI7836 Dose 1 subcutaneous (SC) injection on Day 1. | 6 |
| MEDI7836 Dose 2 Participants received a single-dose of MEDI7836 Dose 2 subcutaneous (SC) injection on Day 1. | 6 |
| MEDI7836 Dose 3 Participants received a single-dose of MEDI7836 Dose 3 subcutaneous (SC) injection on Day 1. | 6 |
| MEDI7836 Dose 4 Participants received a single-dose of MEDI7836 Dose 4 subcutaneous (SC) injection on Day 1. | 6 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | MEDI7836 Dose 1 | MEDI7836 Dose 2 | MEDI7836 Dose 3 | MEDI7836 Dose 4 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 36.4 Years STANDARD_DEVIATION 9.9 | 38.2 Years STANDARD_DEVIATION 7.1 | 32.8 Years STANDARD_DEVIATION 11.5 | 32.8 Years STANDARD_DEVIATION 9.7 | 32.0 Years STANDARD_DEVIATION 14 | 34.6 Years STANDARD_DEVIATION 10.2 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 32 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 8 | 4 / 6 | 6 / 6 | 5 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Treatment-emergent adverse events between first dose of study drug and Day 281 after the last dose that were absent before treatment or that worsened relative to pre-treatment state. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed.
Time frame: From Study Drug Administration to 281 Days Postdose
Population: As Treated Population included all randomized participants and treated with MEDI7836 or placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 0 Participant |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Transaminases increased | 1 Participant |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Platelet count decreased | 0 Participant |
| MEDI7836 Dose 1 | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 0 Participant |
| MEDI7836 Dose 1 | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Platelet count decreased | 1 Participant |
| MEDI7836 Dose 1 | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Transaminases increased | 1 Participant |
| MEDI7836 Dose 2 | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Transaminases increased | 0 Participant |
| MEDI7836 Dose 2 | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Platelet count decreased | 0 Participant |
| MEDI7836 Dose 2 | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 0 Participant |
| MEDI7836 Dose 3 | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Platelet count decreased | 0 Participant |
| MEDI7836 Dose 3 | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Transaminases increased | 0 Participant |
| MEDI7836 Dose 3 | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 1 Participant |
| MEDI7836 Dose 4 | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 1 Participant |
| MEDI7836 Dose 4 | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Platelet count decreased | 0 Participant |
| MEDI7836 Dose 4 | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events | Transaminases increased | 0 Participant |
Primary
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events
AEs observed in participants with clinically significant ECG abnormalities were assessed. ECG parameters included heart rate, RR, PR, QRS, QT and QTc intervals. Treatment-emergent adverse events between administration of investigational product and Day 281 that were absent before treatment or that worsened relative to pre-treatment state.
Time frame: From Study Drug Administration to 281 Days Postdose
Population: As Treated Population included all randomized participants and treated with MEDI7836 or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | 0 Participant |
| MEDI7836 Dose 1 | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | 0 Participant |
| MEDI7836 Dose 2 | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | 0 Participant |
| MEDI7836 Dose 3 | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | 0 Participant |
| MEDI7836 Dose 4 | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | 0 Participant |
Primary
Number of Participants With Injection Site Reactions
Participants were evaluated for manifestations of injection site reactions.
Time frame: From Study Drug Administration to 281 Days Postdose
Population: As Treated Population included all randomized participants and treated with MEDI7836 or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Injection Site Reactions | 4 Participant |
| MEDI7836 Dose 1 | Number of Participants With Injection Site Reactions | 2 Participant |
| MEDI7836 Dose 2 | Number of Participants With Injection Site Reactions | 3 Participant |
| MEDI7836 Dose 3 | Number of Participants With Injection Site Reactions | 0 Participant |
| MEDI7836 Dose 4 | Number of Participants With Injection Site Reactions | 5 Participant |
Primary
Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received MEDI7836. Treatment-emergent adverse events between administration of investigational product and Day 281 that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From Study Drug Administration to 281 Days Postdose
Population: As Treated Population included all randomized participants and treated with MEDI7836 or placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 6 Participant |
| Placebo | Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participant |
| MEDI7836 Dose 1 | Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 4 Participant |
| MEDI7836 Dose 1 | Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participant |
| MEDI7836 Dose 2 | Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participant |
| MEDI7836 Dose 2 | Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 6 Participant |
| MEDI7836 Dose 3 | Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participant |
| MEDI7836 Dose 3 | Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 5 Participant |
| MEDI7836 Dose 4 | Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 6 Participant |
| MEDI7836 Dose 4 | Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participant |
Primary
Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as Treatment-Emergent Adverse Events
Vital sign parameters included blood pressure, temperature, pulse rate, respiratory rate and weight. Physical examination included assessment of general appearance, weight, head, ears, eyes, nose, throat, neck, skin, cardiovascular system, respiratory system, abdominal system, and nervous system. Criteria for abnormal physical findings was based on investigator's discretion. TEAEs were present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug until Day 281 after the last dose of study drug.
Time frame: From Study Drug Administration to 281 Days Postdose
Population: As Treated Population included all randomized participants and treated with MEDI7836 or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as Treatment-Emergent Adverse Events | 0 Participant |
| MEDI7836 Dose 1 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as Treatment-Emergent Adverse Events | 0 Participant |
| MEDI7836 Dose 2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as Treatment-Emergent Adverse Events | 0 Participant |
| MEDI7836 Dose 3 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as Treatment-Emergent Adverse Events | 0 Participant |
| MEDI7836 Dose 4 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as Treatment-Emergent Adverse Events | 0 Participant |
Secondary
Apparent Systemic Clearance (CL/F) of MEDI7836
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
Population: PK Population included all participants who received MEDI7836 had detectable postdose MEDI7836 serum concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Systemic Clearance (CL/F) of MEDI7836 | 616.206 milliliter per day (mL/day) | Standard Deviation 422.587 |
| MEDI7836 Dose 1 | Apparent Systemic Clearance (CL/F) of MEDI7836 | 481.219 milliliter per day (mL/day) | Standard Deviation 282.488 |
| MEDI7836 Dose 2 | Apparent Systemic Clearance (CL/F) of MEDI7836 | 463.827 milliliter per day (mL/day) | Standard Deviation 226.96 |
| MEDI7836 Dose 3 | Apparent Systemic Clearance (CL/F) of MEDI7836 | 706.952 milliliter per day (mL/day) | Standard Deviation 283.588 |
Secondary
Apparent Terminal-Phase Volume of Distribution (Vz/F) of MEDI7836
The apparent volume of distribution of MEDI7836 after a single dose, calculated according to the equation: Vz/F = Apparent total clearance (CL/F) / terminal phase rate constant (λz).
Time frame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
Population: PK Population included all participants who received MEDI7836 had detectable postdose MEDI7836 serum concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Terminal-Phase Volume of Distribution (Vz/F) of MEDI7836 | 18885.105 mL | Standard Deviation 7689.663 |
| MEDI7836 Dose 1 | Apparent Terminal-Phase Volume of Distribution (Vz/F) of MEDI7836 | 15032.685 mL | Standard Deviation 6066.111 |
| MEDI7836 Dose 2 | Apparent Terminal-Phase Volume of Distribution (Vz/F) of MEDI7836 | 22930.365 mL | Standard Deviation 8180.111 |
| MEDI7836 Dose 3 | Apparent Terminal-Phase Volume of Distribution (Vz/F) of MEDI7836 | 36686.872 mL | Standard Deviation 14142.345 |
Secondary
Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) of MEDI7836
Area under the concentration-time curve of the MEDI7836 in serum over the time interval from 0 extrapolated to infinity (AUC0-inf).
Time frame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
Population: Pharmacokinetic (PK) Population included all participants who received MEDI7836 had detectable postdose MEDI7836 serum concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) of MEDI7836 | 62.958 Day*microgram per milliliter | Standard Deviation 29.629 |
| MEDI7836 Dose 1 | Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) of MEDI7836 | 310.805 Day*microgram per milliliter | Standard Deviation 204.858 |
| MEDI7836 Dose 2 | Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) of MEDI7836 | 807.725 Day*microgram per milliliter | Standard Deviation 418.083 |
| MEDI7836 Dose 3 | Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) of MEDI7836 | 1101.742 Day*microgram per milliliter | Standard Deviation 817.295 |
Secondary
Area Under the Concentration-Time Curve From Zero to Last Observation (AUC [0-t]) of MEDI7836
Area under the concentration-time curve of the MEDI7836 in serum over the time interval from 0 to the last quantifiable data point (AUC0-t).
Time frame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
Population: PK Population included all participants who received MEDI7836 had detectable postdose MEDI7836 serum concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-Time Curve From Zero to Last Observation (AUC [0-t]) of MEDI7836 | 62.106 day*mcg/mL | Standard Deviation 29.237 |
| MEDI7836 Dose 1 | Area Under the Concentration-Time Curve From Zero to Last Observation (AUC [0-t]) of MEDI7836 | 308.965 day*mcg/mL | Standard Deviation 203.367 |
| MEDI7836 Dose 2 | Area Under the Concentration-Time Curve From Zero to Last Observation (AUC [0-t]) of MEDI7836 | 799.769 day*mcg/mL | Standard Deviation 406.585 |
| MEDI7836 Dose 3 | Area Under the Concentration-Time Curve From Zero to Last Observation (AUC [0-t]) of MEDI7836 | 1096.620 day*mcg/mL | Standard Deviation 807.266 |
Secondary
Maximum Observed Serum Concentration (Cmax) of MEDI7836
The Cmax is the maximum observed serum concentration of study drug.
Time frame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
Population: PK Population included all participants who received MEDI7836 had detectable postdose MEDI7836 serum concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Serum Concentration (Cmax) of MEDI7836 | 1.587 microgram per milliliter (mcg/mL) | Standard Deviation 0.436 |
| MEDI7836 Dose 1 | Maximum Observed Serum Concentration (Cmax) of MEDI7836 | 10.435 microgram per milliliter (mcg/mL) | Standard Deviation 1.52 |
| MEDI7836 Dose 2 | Maximum Observed Serum Concentration (Cmax) of MEDI7836 | 24.600 microgram per milliliter (mcg/mL) | Standard Deviation 5.313 |
| MEDI7836 Dose 3 | Maximum Observed Serum Concentration (Cmax) of MEDI7836 | 41.933 microgram per milliliter (mcg/mL) | Standard Deviation 7.208 |
Secondary
Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836
A participant was considered ADA-positive across the study if they had a positive reading at any time point during the study.
Time frame: Predose on Day 1 to 281 days Postdose
Population: As Treated Population included all randomized participants and treated with MEDI7836 or placebo. Here, n is number of participants analysed at given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836 | Baseline (n=8,6,6,6,6) | 25.0 Percentage of participant |
| Placebo | Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836 | Post-Baseline Day 281 (n=8,6,5,6,6) | 12.5 Percentage of participant |
| MEDI7836 Dose 1 | Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836 | Baseline (n=8,6,6,6,6) | 33.3 Percentage of participant |
| MEDI7836 Dose 1 | Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836 | Post-Baseline Day 281 (n=8,6,5,6,6) | 66.7 Percentage of participant |
| MEDI7836 Dose 2 | Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836 | Baseline (n=8,6,6,6,6) | 66.7 Percentage of participant |
| MEDI7836 Dose 2 | Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836 | Post-Baseline Day 281 (n=8,6,5,6,6) | 20.0 Percentage of participant |
| MEDI7836 Dose 3 | Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836 | Post-Baseline Day 281 (n=8,6,5,6,6) | 50.0 Percentage of participant |
| MEDI7836 Dose 3 | Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836 | Baseline (n=8,6,6,6,6) | 50.0 Percentage of participant |
| MEDI7836 Dose 4 | Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836 | Baseline (n=8,6,6,6,6) | 50.0 Percentage of participant |
| MEDI7836 Dose 4 | Percentage of Participants Positive for Anti-Drug Antibodies to MEDI7836 | Post-Baseline Day 281 (n=8,6,5,6,6) | 50.0 Percentage of participant |
Secondary
Terminal Phase Elimination Half Life (T1/2) of MEDI7836
Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum.
Time frame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
Population: PK Population included all participants who received MEDI7836 had detectable postdose MEDI7836 serum concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Terminal Phase Elimination Half Life (T1/2) of MEDI7836 | 26.988 day | Standard Deviation 14.902 |
| MEDI7836 Dose 1 | Terminal Phase Elimination Half Life (T1/2) of MEDI7836 | 28.091 day | Standard Deviation 14.121 |
| MEDI7836 Dose 2 | Terminal Phase Elimination Half Life (T1/2) of MEDI7836 | 36.944 day | Standard Deviation 9.329 |
| MEDI7836 Dose 3 | Terminal Phase Elimination Half Life (T1/2) of MEDI7836 | 37.013 day | Standard Deviation 5.185 |
Secondary
Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI7836
The Tmax is defined as actual sampling time to reach maximum observed MEDI7836 concentration.
Time frame: Predose on Day 1 and on Days 2, 3, 4, 6, 8, 10, 15, 29, 43, 57, 85, 113, 169, 225 and 281 Postdose
Population: PK Population included all participants who received MEDI7836 had detectable postdose MEDI7836 serum concentrations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI7836 | 4.0 day |
| MEDI7836 Dose 1 | Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI7836 | 5.0 day |
| MEDI7836 Dose 2 | Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI7836 | 5.0 day |
| MEDI7836 Dose 3 | Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI7836 | 6.0 day |