Obesity
Conditions
Brief summary
The study aims to assess the safety and tolerability of maridebart cafraglutide as single and multiple doses in participants with obesity
Interventions
BIOLOGICALmaridebart cafraglutide
Participants will receive maridebart cafraglutide as a single dose in Part A and multiple doses in Part B and C.
DRUGPlacebo
Participants will receive placebo as a single dose in Part A and multiple doses in Part B.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participant has provided informed consent before initiation of any study-specific activities/procedures. * Age ≥ 18 years to ≤ 65 years, at the time of signing the informed consent. * Except for obesity, otherwise healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and ECGs on day -2 (cohorts 1-6, cohort 11-13) or day -1 (cohorts 7-10) and screening. * Body mass index between ≥ 30.0 kg/m\^2 and ≤ 40.0 kg/m\^2. * Have a stable body weight (\< 5 kg self-reported change during the previous 8 weeks) before screening. * Willing to maintain current general diet and physical activity regimen, except for the physical activity in the 72 hours before each blood sample collection for the clinical laboratory analysis, which should not be strenuous. * Females must be of nonreproductive potential • Postmenopausal as defined as: * Age of ≥ 55 years with no menses for at least 12 months; OR * Age \< 55 years with no menses for at least 12 months AND with a follicle-stimulating hormone level \> 40 IU/L or according to the definition of postmenopausal range for the laboratory involved; OR * History of hysterectomy; OR * History of bilateral oophorectomy. * For patients in cohorts 7-10 only, participants must have a smartphone device with the capability of downloading apps or other digital tools required for this cohort.
Exclusion criteria
* History or clinical evidence of diabetes mellitus, including hemoglobin A1c (HbA1c) \> 6.5% and/or a fasting glucose ≥ 125 mg/dl (6.9 mmol/L) at screening. * Triglycerides ≥ 5.65 mmol/L (ie, 500 mg/dL) at screening. * Screening calcitonin ≥ 50 ng/L. * Hepatic liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or total bilirubin levels \> 1.5 times the upper limit of normal (ULN) at screening. If ALT is \> 1.5 x the ULN at screening AND the AST, alkaline phosphatase, and total bilirubin levels are within normal limits, then participant may be eligible for enrollment after a discussion with the medical monitor. * History or clinical evidence of bleeding diathesis or any coagulation disorder, including prothrombin time (PT), activated partial thromboplastin time (PTT), international normalized ratio (INR), or platelet count outside of the laboratory's normal reference range at screening. If a single value (PT, PTT, INR, or platelet count) is outside the normal reference range at screening and the participant does not have evidence of any other bleeding or coagulation disorder, then the participant may be eligible for enrollment after a discussion with the medical monitor. * History of gastrointestinal abnormality that could affect gastrointestinal motility (including small bowel or colonic resection, inflammatory bowel disease, irritable bowel disease, and colon or gastrointestinal tract cancer). * Participants with a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 or a personal history of nonfamilial medullary thyroid carcinoma. * Participants with a history of confirmed chronic pancreatitis or idiopathic acute pancreatitis. * Participants with a history of gall bladder disease (ie, cholelithiasis or cholecystitis) not treated with cholecystectomy. * Untreated or uncontrolled hypothyroidism/hyperthyroidism defined as thyroid stimulating hormone \> 6 mIU/L or \<0.4 mIU/L. * A corrected QT interval (QTc) at screening of \> 450 msec in males or \> 470 msec in females or history of long QT syndrome. * Participants with a history of renal impairment or renal disease and/or estimated glomerular filtration rate ≤ 60 mL/min/1.73 m\^2. * Obesity induced by other endocrinologic disorders (eg, Cushing's Syndrome). * Previous surgical treatment for obesity (excluding liposuction if performed \>1 year before study entry) and/or participants with recent (within 6 months) or planned endoscopic treatment for obesity. * History of major depressive disorder. * History of other severe psychiatric disorders, eg schizophrenia, bipolar disorder. * Any lifetime history of a suicidal attempt or of any suicidal behavior. * Surgery scheduled for the study duration period, except for minor surgical procedures, at the discretion of the investigator. * Positive results for human immunodeficiency virus antibodies, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus RNA. For hepatitis C, hepatitis C antibody testing is done at screening, followed by hepatitis C virus RNA by polymerase chain reaction if hepatitis C antibody is positive. * Systolic blood pressure ≥ 150 mm Hg or diastolic blood pressure ≥ 90 mm Hg at screening, or on day -2. For each visit, if the initial blood pressure is elevated, the reading may be repeated once at least 15 minutes later and the lower of the 2 readings may be used. * History of malignancy of any type, other than in situ cervical cancer or surgically excised nonmelanomatous skin cancers occurring more than 5 years before randomization. * Use of the following agents are excluded unless there is a prior consultation between the investigator and Amgen medical monitor: * Prescription and nonprescription drugs within 14 days or 5 half-lives, whichever is longer, before the first dose of investigational product, with exception of hormone replacement therapy (eg, estrogen, thyroid). * All herbal medicines, vitamins, and supplements within 30 days before receiving the first dose of investigational product. * Exceptions must be reviewed and approved by the investigator and Amgen medical monitor. Written documentation of this review and Amgen acknowledgment is required for participant participation. * Current or history of treatment with medications that may cause significant weight gain or loss, within 3 months before screening, including systemic corticosteroids (except for a short course of treatment, ie, 7 to 10 days), tricyclic antidepressants, atypical antipsychotic and mood stabilizers (eg, imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium). * Current participation (or within the last 3 months) in an organized weight reduction program or currently using or used within 3 months before screening: pramlintide, sibutramine, orlistat, zonisamide, topiramate, phentermine, naltrexone, bupropion, lorcaserin, metformin, or any GLP-1R agonists (either by prescription or as part of a clinical study). * Prior exposure to maridebart cafraglutide or AMG 598 or currently receiving treatment in another investigational device or drug study, or less than 5 half-lives since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. * Female participants with a positive pregnancy test assessed at screening and/or day -2 by a serum pregnancy test and/or urine pregnancy test) or female participants who are breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 5 months after the last dose of maridebart cafraglutide. * Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use an acceptable method of contraception during treatment and for an additional 5 months after the last dose of maridebart cafraglutide. * Male participants unwilling to abstain from donating sperm during treatment and for an additional 5 months after the last dose of maridebart cafraglutide. * Participant has known sensitivity to maridebart cafraglutide or components thereof or a history of drug or other allergy that is in the opinion of the investigator or medical monitor (if appropriate), contraindicates their participation. * Participant has a known sensitivity to GLP-1R agonists. * Participant has known sensitivity to mammalian derived products. * Participant has an allergy or known sensitivity to acetaminophen. * Participant is unwilling or unable to limit alcohol consumption throughout the course of the study. Alcohol is prohibited 48 hours before day -2 and is limited to no more than to 2 drinks per day for males and 1 drink per day for females for the duration of the study (1 drink being equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt liquor, 5 ounces of wine, or 1.5 ounces of 80 proof distilled spirits). * Participant uses nicotine or tobacco containing products (including but not limited to: snuff, chewing tobacco, cigars, cigarettes, e-cigarettes, pipes, or nicotine patches) within 6 months before screening. Participant is unwilling or unable to abstain from nicotine or tobacco, cigars, cigarettes, pipes, or nicotine patches throughout the course of the study. * Participant is tested positive for alcohol and/or drugs of abuse at screening. * History of substance abuse (ie, alcohol, licit or illicit drugs) within 12 months before screening. * Participant is unwilling to refrain from strenuous exercise (eg, heavy lifting, weight training, and aerobics) for 72 hours before each blood collection for clinical laboratory tests. * Participant has donated or lost ≥ 500 mL of blood or plasma within 60 days of day -2. * Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge. * History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion. * For participants in cohorts 7-10 and cohorts 12-13 only, the Patient Health Questionnaire-9 (PHQ-9) score of ≥ 10 up to day 1. * For participants in cohorts 7-10 and 12-13 only, any suicidal ideation as identified by endorsement of (answered yes to) any of the items numbered 1-5 on the Columbia Suicide Severity Rating Scale (C-SSRS) up to day 1. * For participants in cohorts 7-10 and 12-13 only, participant has systolic blood pressure ≥ 150 mm Hg or diastolic blood pressure ≥ 95 mm Hg on day 1. For each visit, if the initial blood pressure is elevated, the reading may be repeated once at least 15 minutes later and the lower of the 2 readings may be used. * For participants in cohorts 7-10 and 12-13 only, a QTc of \> 450 msec in males or \> 470 msec in females up to day 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Part A: 150 days; Part B: 207 days; Part C Cohort 12: 193 days; Part C Cohort 13: 207 days | A TEAE was defined as any adverse event (AE) which started on or after the first dose of AMG 133. Clinically significant changes in laboratory safety tests, vital signs and 12-lead electrocardiograms (ECGs) were included as AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Cmax of AMG 133 | Cohorts 7-9: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 36, 43, 50, 57 (predose), 61, 63, 71, 78, 85, 127, 169 and 207. Cohort 10: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 36, 43, 50, 57 (predose), 63, 71, 78, 85, 169 and 207 | The pharmacokinetic parameter estimates of intact and total AMG 133 after multiple administrations of AMG 133 were reported. |
| Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Cohort 1-5, 11: Day 1 predose and 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 43, 57, 71, 92, 120 and 150. Cohort 6: Day 1 predose and 10 mins, 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 15, 22, 29, 43, 57, 71, 92, 120 and 150 | The pharmacokinetic parameter estimates of intact and total AMG 133 after a single administration of AMG 133 were reported. |
| Part B: Tmax of AMG 133 | Cohorts 7-9: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 36, 43, 50, 57 (predose), 61, 63, 71, 78, 85, 127, 169 and 207. Cohort 10: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 36, 43, 50, 57 (predose), 63, 71, 78, 85, 169 and 207 | The pharmacokinetic parameter estimates of intact and total AMG 133 after multiple administrations of AMG 133 were reported. |
| Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Cohort 1-5, 11: Day 1 predose and 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 43, 57, 71, 92, 120 and 150. Cohort 6: Day 1 predose and 10 mins, 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 15, 22, 29, 43, 57, 71, 92, 120 and 150 | The pharmacokinetic parameter estimates of intact and total AMG 133 after a single administration of AMG 133 were reported. |
| Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Cohorts 7-9: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 57 (predose), 61, 63, 71, 78 and 85. Cohort 10: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 57 (predose), 63, 71, 78 and 85 | The pharmacokinetic parameter estimates of intact and total AMG 133 after multiple administrations of AMG 133 were reported. This parameter shows the AUC over the 28-day dosing interval, both from Day 1 to Day 29 (predose) and from Day 57 to Day 85. |
| Percentage of Participants With Anti-AMG 133 Antibody Formation | Part A Cohort 1-6 and 11: Up to Day 150. Part B Cohort 7-10 and Part C Cohort 13: Up to Day 207. Part C Cohort 12: Up to Day 193 | The percentage of participants who developed anti-AMG 133 antibodies (binding and if positive, neutralizing to native GLP-1, when available) at any time was presented. |
| Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Cohort 1-5, 11: Day 1 predose and 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 43, 57, 71, 92, 120 and 150. Cohort 6: Day 1 predose and 10 mins, 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 15, 22, 29, 43, 57, 71, 92, 120 and 150 | The pharmacokinetic parameter estimates of intact and total AMG 133 after a single administration of AMG 133 were reported. |
Countries
United States
Participant flow
Recruitment details
A total of 110 participants were enrolled into this trial in the United States between August 2020 and November 2022.
Pre-assignment details
This trial comprised three parts: Parts A and B were randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) phases, respectively; and part C was an open-label, modified, MAD phase.
Participants by arm
| Arm | Count |
|---|---|
| Part A SAD Cohort 1 AMG 133 Participants received a single dose of 21 mg AMG 133 SC. | 6 |
| Part A SAD Cohort 2 AMG 133 Participants received a single dose of 70 mg AMG 133 SC. | 6 |
| Part A SAD Cohort 3 AMG 133 Participants received a single dose of 140 mg AMG 133 SC. | 7 |
| Part A SAD Cohort 4 AMG 133 Participants received a single dose of 280 mg AMG 133 SC. | 6 |
| Part A SAD Cohort 5 AMG 133 Participants received a single dose of 560 mg AMG 133 SC. | 6 |
| Part A SAD Cohort 6 AMG 133 Participants received a single dose of 70 mg AMG 133 IV. | 6 |
| Part A SAD SC Placebo (Cohorts 1-5, 11) Participants received a single dose of placebo SC. | 12 |
| Part A SAD IV Placebo (Cohort 6) Participants received a single dose of placebo IV. | 2 |
| Part B MAD Cohort 7 AMG 133 Participants received multiple doses of 140 mg AMG 133 SC Q4W. | 6 |
| Part B MAD Cohort 8 AMG 133 Participants received multiple doses of 280 mg AMG 133 SC Q4W. | 6 |
| Part B MAD Cohort 9 AMG 133 Participants received multiple doses of 560 mg AMG 133 SC Q4W. | 8 |
| Part B MAD Cohort 10 AMG 133 Participants received multiple doses of 560 mg AMG 133 SC Q4W. This cohort included the use of digital health tools. | 10 |
| Part B MAD Cohorts 7-9 Placebo Participants received multiple doses of placebo SC Q4W. | 6 |
| Part B MAD Cohort 10 Placebo Participants received multiple doses of placebo SC Q4W. This cohort included the use of digital health tools. | 3 |
| Part A SAD Cohort 11 AMG 133 Participants received a single dose of 840 mg AMG 133 SC. | 6 |
| Part C MAD Cohort 12 Participants received 2 doses of 70 mg AMG 133 SC QW, then 2 doses of 420 mg AMG 133 SC Q4W. | 6 |
| Part C MAD Cohort 13 Participants received 4 doses of 70 mg AMG 133 SC QW, then 2 doses of 420 mg AMG 133 SC Q4W. | 8 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 2 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal of consent from study | 0 | 1 | 2 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 4 | 3 | 0 | 0 | 1 | 0 | 4 |
Baseline characteristics
| Characteristic | Total | Part A SAD Cohort 2 AMG 133 | Part A SAD Cohort 3 AMG 133 | Part A SAD Cohort 4 AMG 133 | Part A SAD Cohort 5 AMG 133 | Part A SAD Cohort 1 AMG 133 | Part A SAD Cohort 6 AMG 133 | Part A SAD SC Placebo (Cohorts 1-5, 11) | Part A SAD IV Placebo (Cohort 6) | Part B MAD Cohort 7 AMG 133 | Part B MAD Cohort 8 AMG 133 | Part B MAD Cohort 9 AMG 133 | Part B MAD Cohort 10 AMG 133 | Part B MAD Cohorts 7-9 Placebo | Part B MAD Cohort 10 Placebo | Part A SAD Cohort 11 AMG 133 | Part C MAD Cohort 12 | Part C MAD Cohort 13 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 109 Participants | 6 Participants | 7 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 12 Participants | 2 Participants | 6 Participants | 6 Participants | 8 Participants | 10 Participants | 6 Participants | 3 Participants | 6 Participants | 6 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 10 Participants | 2 Participants | 3 Participants | 5 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants | 4 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 7 Participants | 0 Participants | 4 Participants | 2 Participants | 4 Participants | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 33 Participants | 2 Participants | 5 Participants | 3 Participants | 0 Participants | 2 Participants | 5 Participants | 4 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 72 Participants | 4 Participants | 2 Participants | 3 Participants | 5 Participants | 4 Participants | 1 Participants | 8 Participants | 2 Participants | 2 Participants | 5 Participants | 7 Participants | 10 Participants | 5 Participants | 3 Participants | 5 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 47 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 5 Participants | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 2 Participants | 7 Participants | 5 Participants | 4 Participants | 1 Participants | 1 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Male | 63 Participants | 5 Participants | 4 Participants | 4 Participants | 5 Participants | 1 Participants | 4 Participants | 8 Participants | 2 Participants | 5 Participants | 4 Participants | 1 Participants | 5 Participants | 2 Participants | 2 Participants | 5 Participants | 1 Participants | 5 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 10 | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 0 / 6 | 2 / 6 | 5 / 7 | 6 / 6 | 5 / 6 | 6 / 6 | 3 / 12 | 1 / 2 | 6 / 6 | 6 / 6 | 8 / 8 | 8 / 10 | 3 / 6 | 0 / 3 | 6 / 6 | 5 / 6 | 6 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 10 | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
A TEAE was defined as any adverse event (AE) which started on or after the first dose of AMG 133. Clinically significant changes in laboratory safety tests, vital signs and 12-lead electrocardiograms (ECGs) were included as AEs.
Time frame: Part A: 150 days; Part B: 207 days; Part C Cohort 12: 193 days; Part C Cohort 13: 207 days
Population: Full analysis set: all randomized participants who received at least one dose of AMG 133 or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A SAD Cohort 1 AMG 133 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 0 participants |
| Part A SAD Cohort 2 AMG 133 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 2 participants |
| Part A SAD Cohort 3 AMG 133 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 participants |
| Part A SAD Cohort 4 AMG 133 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 participants |
| Part A SAD Cohort 5 AMG 133 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 participants |
| Part A SAD Cohort 6 AMG 133 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 participants |
| Part A SAD Cohort 11 AMG 133 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 participants |
| Part A SAD IV Placebo (Cohort 6) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 participants |
| Part B MAD Cohort 7 AMG 133 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 participants |
| Part B MAD Cohort 8 AMG 133 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 participants |
| Part B MAD Cohort 9 AMG 133 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 8 participants |
| Part B MAD Cohort 10 AMG 133 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 8 participants |
| Part B MAD Cohorts 7-9 Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 participants |
| Part B MAD Cohort 10 Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 0 participants |
| Part A SAD Cohort 11 AMG 133 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 participants |
| Part C MAD Cohort 12 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 participants |
| Part C MAD Cohort 13 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 participants |
Secondary
Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133
The pharmacokinetic parameter estimates of intact and total AMG 133 after a single administration of AMG 133 were reported.
Time frame: Cohort 1-5, 11: Day 1 predose and 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 43, 57, 71, 92, 120 and 150. Cohort 6: Day 1 predose and 10 mins, 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 15, 22, 29, 43, 57, 71, 92, 120 and 150
Population: Pharmacokinetics analysis set: all participants who received at least 1 dose of AMG 133 for whom at least 1 pharmacokinetics parameter could be adequately estimated. Participants with data available at each timepoint are presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A SAD Cohort 1 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Intact AMG 133 | 39.0 mcg*day/mL | Standard Deviation 13.6 |
| Part A SAD Cohort 1 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Total AMG 133 | 56.4 mcg*day/mL | Standard Deviation 20.3 |
| Part A SAD Cohort 2 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Intact AMG 133 | 108 mcg*day/mL | Standard Deviation 35.2 |
| Part A SAD Cohort 2 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Total AMG 133 | 151 mcg*day/mL | Standard Deviation 51.2 |
| Part A SAD Cohort 3 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Intact AMG 133 | 230 mcg*day/mL | Standard Deviation 56.2 |
| Part A SAD Cohort 3 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Total AMG 133 | 300 mcg*day/mL | Standard Deviation 104 |
| Part A SAD Cohort 4 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Intact AMG 133 | 442 mcg*day/mL | Standard Deviation 263 |
| Part A SAD Cohort 4 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Total AMG 133 | 629 mcg*day/mL | Standard Deviation 375 |
| Part A SAD Cohort 5 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Intact AMG 133 | 762 mcg*day/mL | Standard Deviation 196 |
| Part A SAD Cohort 5 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Total AMG 133 | 1100 mcg*day/mL | Standard Deviation 321 |
| Part A SAD Cohort 6 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Intact AMG 133 | 205 mcg*day/mL | Standard Deviation 67.9 |
| Part A SAD Cohort 6 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Total AMG 133 | 264 mcg*day/mL | Standard Deviation 112 |
| Part A SAD Cohort 11 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Intact AMG 133 | 1150 mcg*day/mL | Standard Deviation 280 |
| Part A SAD Cohort 11 AMG 133 | Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133 | Total AMG 133 | 1720 mcg*day/mL | Standard Deviation 468 |
Secondary
Part A: Maximum Observed Concentration (Cmax) of AMG 133
The pharmacokinetic parameter estimates of intact and total AMG 133 after a single administration of AMG 133 were reported.
Time frame: Cohort 1-5, 11: Day 1 predose and 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 43, 57, 71, 92, 120 and 150. Cohort 6: Day 1 predose and 10 mins, 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 15, 22, 29, 43, 57, 71, 92, 120 and 150
Population: Pharmacokinetics analysis set: all participants who received at least 1 dose of AMG 133 for whom at least 1 pharmacokinetics parameter could be adequately estimated. Participants with data available at each timepoint are presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A SAD Cohort 1 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Intact AMG 133 | 1.31 µg/mL | Standard Deviation 0.559 |
| Part A SAD Cohort 1 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Total AMG 133 | 1.43 µg/mL | Standard Deviation 0.614 |
| Part A SAD Cohort 2 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Total AMG 133 | 3.68 µg/mL | Standard Deviation 1.16 |
| Part A SAD Cohort 2 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Intact AMG 133 | 3.42 µg/mL | Standard Deviation 1.18 |
| Part A SAD Cohort 3 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Total AMG 133 | 6.78 µg/mL | Standard Deviation 3.16 |
| Part A SAD Cohort 3 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Intact AMG 133 | 6.09 µg/mL | Standard Deviation 2.8 |
| Part A SAD Cohort 4 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Intact AMG 133 | 15.7 µg/mL | Standard Deviation 11.4 |
| Part A SAD Cohort 4 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Total AMG 133 | 17.1 µg/mL | Standard Deviation 11.8 |
| Part A SAD Cohort 5 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Intact AMG 133 | 35.8 µg/mL | Standard Deviation 10.3 |
| Part A SAD Cohort 5 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Total AMG 133 | 37.7 µg/mL | Standard Deviation 12.5 |
| Part A SAD Cohort 6 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Intact AMG 133 | 22.7 µg/mL | Standard Deviation 4.1 |
| Part A SAD Cohort 6 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Total AMG 133 | 22.9 µg/mL | Standard Deviation 4.21 |
| Part A SAD Cohort 11 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Intact AMG 133 | 41.5 µg/mL | Standard Deviation 7.35 |
| Part A SAD Cohort 11 AMG 133 | Part A: Maximum Observed Concentration (Cmax) of AMG 133 | Total AMG 133 | 43.2 µg/mL | Standard Deviation 7.07 |
Secondary
Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133
The pharmacokinetic parameter estimates of intact and total AMG 133 after a single administration of AMG 133 were reported.
Time frame: Cohort 1-5, 11: Day 1 predose and 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 43, 57, 71, 92, 120 and 150. Cohort 6: Day 1 predose and 10 mins, 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 15, 22, 29, 43, 57, 71, 92, 120 and 150
Population: Pharmacokinetics analysis set: all participants who received at least 1 dose of AMG 133 for whom at least 1 pharmacokinetics parameter could be adequately estimated. Participants with data available at each timepoint are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A SAD Cohort 1 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Intact AMG 133 | 5.0 days |
| Part A SAD Cohort 1 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Total AMG 133 | 5.9 days |
| Part A SAD Cohort 2 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Intact AMG 133 | 4.9 days |
| Part A SAD Cohort 2 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Total AMG 133 | 4.9 days |
| Part A SAD Cohort 3 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Intact AMG 133 | 6.0 days |
| Part A SAD Cohort 3 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Total AMG 133 | 7.0 days |
| Part A SAD Cohort 4 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Intact AMG 133 | 5.8 days |
| Part A SAD Cohort 4 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Total AMG 133 | 6.9 days |
| Part A SAD Cohort 5 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Intact AMG 133 | 3.9 days |
| Part A SAD Cohort 5 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Total AMG 133 | 4.4 days |
| Part A SAD Cohort 6 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Intact AMG 133 | 0.025 days |
| Part A SAD Cohort 6 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Total AMG 133 | 0.043 days |
| Part A SAD Cohort 11 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Intact AMG 133 | 5.4 days |
| Part A SAD Cohort 11 AMG 133 | Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133 | Total AMG 133 | 5.9 days |
Secondary
Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133
The pharmacokinetic parameter estimates of intact and total AMG 133 after multiple administrations of AMG 133 were reported. This parameter shows the AUC over the 28-day dosing interval, both from Day 1 to Day 29 (predose) and from Day 57 to Day 85.
Time frame: Cohorts 7-9: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 57 (predose), 61, 63, 71, 78 and 85. Cohort 10: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 57 (predose), 63, 71, 78 and 85
Population: Pharmacokinetics analysis set: all participants who received at least 1 dose of AMG 133 for whom at least 1 pharmacokinetics parameter could be adequately estimated. Participants with data available at each timepoint are presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A SAD Cohort 1 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Intact AMG 133 after dosing on Day 1 up to Day 29 | 149 mcg*day/mL | Standard Deviation 23.5 |
| Part A SAD Cohort 1 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Total AMG 133 after dosing on Day 1 up to Day 29 | 181 mcg*day/mL | Standard Deviation 26 |
| Part A SAD Cohort 1 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Intact AMG 133 after dosing on Day 57 up to Day 85 | 214 mcg*day/mL | Standard Deviation 18.7 |
| Part A SAD Cohort 1 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Total AMG 133 after dosing on Day 57 up to Day 85 | 297 mcg*day/mL | Standard Deviation 27.7 |
| Part A SAD Cohort 2 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Total AMG 133 after dosing on Day 1 up to Day 29 | 300 mcg*day/mL | Standard Deviation 122 |
| Part A SAD Cohort 2 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Intact AMG 133 after dosing on Day 57 up to Day 85 | 443 mcg*day/mL | Standard Deviation 136 |
| Part A SAD Cohort 2 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Total AMG 133 after dosing on Day 57 up to Day 85 | 599 mcg*day/mL | Standard Deviation 224 |
| Part A SAD Cohort 2 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Intact AMG 133 after dosing on Day 1 up to Day 29 | 246 mcg*day/mL | Standard Deviation 95.5 |
| Part A SAD Cohort 3 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Intact AMG 133 after dosing on Day 57 up to Day 85 | 1220 mcg*day/mL | Standard Deviation 432 |
| Part A SAD Cohort 3 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Total AMG 133 after dosing on Day 1 up to Day 29 | 697 mcg*day/mL | Standard Deviation 244 |
| Part A SAD Cohort 3 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Total AMG 133 after dosing on Day 57 up to Day 85 | 1610 mcg*day/mL | Standard Deviation 624 |
| Part A SAD Cohort 3 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Intact AMG 133 after dosing on Day 1 up to Day 29 | 594 mcg*day/mL | Standard Deviation 201 |
| Part A SAD Cohort 4 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Total AMG 133 after dosing on Day 57 up to Day 85 | 691 mcg*day/mL | Standard Deviation 114 |
| Part A SAD Cohort 4 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Total AMG 133 after dosing on Day 1 up to Day 29 | 419 mcg*day/mL | Standard Deviation 43.7 |
| Part A SAD Cohort 4 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Intact AMG 133 after dosing on Day 1 up to Day 29 | 347 mcg*day/mL | Standard Deviation 28.7 |
| Part A SAD Cohort 4 AMG 133 | Part B: AUC From Day 0 to 28 (AUC0-28) of AMG 133 | Intact AMG 133 after dosing on Day 57 up to Day 85 | 512 mcg*day/mL | Standard Deviation 79.7 |
Secondary
Part B: Cmax of AMG 133
The pharmacokinetic parameter estimates of intact and total AMG 133 after multiple administrations of AMG 133 were reported.
Time frame: Cohorts 7-9: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 36, 43, 50, 57 (predose), 61, 63, 71, 78, 85, 127, 169 and 207. Cohort 10: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 36, 43, 50, 57 (predose), 63, 71, 78, 85, 169 and 207
Population: Pharmacokinetics analysis set: all participants who received at least 1 dose of AMG 133 for whom at least 1 pharmacokinetics parameter could be adequately estimated. Participants with data available at each timepoint are presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A SAD Cohort 1 AMG 133 | Part B: Cmax of AMG 133 | Intact AMG 133 after dosing on Day 1 | 8.30 µg/mL | Standard Deviation 2.59 |
| Part A SAD Cohort 1 AMG 133 | Part B: Cmax of AMG 133 | Total AMG 133 after dosing on Day 1 | 8.75 µg/mL | Standard Deviation 2.56 |
| Part A SAD Cohort 1 AMG 133 | Part B: Cmax of AMG 133 | Intact AMG 133 after dosing on Day 57 | 10.4 µg/mL | Standard Deviation 2.19 |
| Part A SAD Cohort 1 AMG 133 | Part B: Cmax of AMG 133 | Total AMG 133 after dosing on Day 57 | 13.1 µg/mL | Standard Deviation 2.86 |
| Part A SAD Cohort 2 AMG 133 | Part B: Cmax of AMG 133 | Total AMG 133 after dosing on Day 1 | 16.2 µg/mL | Standard Deviation 6.52 |
| Part A SAD Cohort 2 AMG 133 | Part B: Cmax of AMG 133 | Intact AMG 133 after dosing on Day 57 | 21.9 µg/mL | Standard Deviation 6.47 |
| Part A SAD Cohort 2 AMG 133 | Part B: Cmax of AMG 133 | Total AMG 133 after dosing on Day 57 | 27.1 µg/mL | Standard Deviation 8.12 |
| Part A SAD Cohort 2 AMG 133 | Part B: Cmax of AMG 133 | Intact AMG 133 after dosing on Day 1 | 14.5 µg/mL | Standard Deviation 5.99 |
| Part A SAD Cohort 3 AMG 133 | Part B: Cmax of AMG 133 | Intact AMG 133 after dosing on Day 57 | 65.1 µg/mL | Standard Deviation 20.4 |
| Part A SAD Cohort 3 AMG 133 | Part B: Cmax of AMG 133 | Total AMG 133 after dosing on Day 1 | 30.1 µg/mL | Standard Deviation 12.3 |
| Part A SAD Cohort 3 AMG 133 | Part B: Cmax of AMG 133 | Total AMG 133 after dosing on Day 57 | 80.8 µg/mL | Standard Deviation 23.2 |
| Part A SAD Cohort 3 AMG 133 | Part B: Cmax of AMG 133 | Intact AMG 133 after dosing on Day 1 | 27.4 µg/mL | Standard Deviation 12.4 |
| Part A SAD Cohort 4 AMG 133 | Part B: Cmax of AMG 133 | Total AMG 133 after dosing on Day 57 | 33.2 µg/mL | Standard Deviation 6.77 |
| Part A SAD Cohort 4 AMG 133 | Part B: Cmax of AMG 133 | Total AMG 133 after dosing on Day 1 | 18.8 µg/mL | Standard Deviation 5.15 |
| Part A SAD Cohort 4 AMG 133 | Part B: Cmax of AMG 133 | Intact AMG 133 after dosing on Day 1 | 17.8 µg/mL | Standard Deviation 5.32 |
| Part A SAD Cohort 4 AMG 133 | Part B: Cmax of AMG 133 | Intact AMG 133 after dosing on Day 57 | 27.2 µg/mL | Standard Deviation 5.2 |
Secondary
Part B: Tmax of AMG 133
The pharmacokinetic parameter estimates of intact and total AMG 133 after multiple administrations of AMG 133 were reported.
Time frame: Cohorts 7-9: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 36, 43, 50, 57 (predose), 61, 63, 71, 78, 85, 127, 169 and 207. Cohort 10: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 36, 43, 50, 57 (predose), 63, 71, 78, 85, 169 and 207
Population: Pharmacokinetics analysis set: all participants who received at least 1 dose of AMG 133 for whom at least 1 pharmacokinetics parameter could be adequately estimated. Participants with data available at each timepoint are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A SAD Cohort 1 AMG 133 | Part B: Tmax of AMG 133 | Intact AMG 133 after dosing on Day 1 | 5.9 days |
| Part A SAD Cohort 1 AMG 133 | Part B: Tmax of AMG 133 | Total AMG 133 after dosing on Day 1 | 6.0 days |
| Part A SAD Cohort 1 AMG 133 | Part B: Tmax of AMG 133 | Intact AMG 133 after dosing on Day 57 | 4.7 days |
| Part A SAD Cohort 1 AMG 133 | Part B: Tmax of AMG 133 | Total AMG 133 after dosing on Day 57 | 5.6 days |
| Part A SAD Cohort 2 AMG 133 | Part B: Tmax of AMG 133 | Total AMG 133 after dosing on Day 1 | 6.0 days |
| Part A SAD Cohort 2 AMG 133 | Part B: Tmax of AMG 133 | Intact AMG 133 after dosing on Day 57 | 4.3 days |
| Part A SAD Cohort 2 AMG 133 | Part B: Tmax of AMG 133 | Total AMG 133 after dosing on Day 57 | 6.2 days |
| Part A SAD Cohort 2 AMG 133 | Part B: Tmax of AMG 133 | Intact AMG 133 after dosing on Day 1 | 6.0 days |
| Part A SAD Cohort 3 AMG 133 | Part B: Tmax of AMG 133 | Intact AMG 133 after dosing on Day 57 | 4.1 days |
| Part A SAD Cohort 3 AMG 133 | Part B: Tmax of AMG 133 | Total AMG 133 after dosing on Day 1 | 5.9 days |
| Part A SAD Cohort 3 AMG 133 | Part B: Tmax of AMG 133 | Total AMG 133 after dosing on Day 57 | 4.1 days |
| Part A SAD Cohort 3 AMG 133 | Part B: Tmax of AMG 133 | Intact AMG 133 after dosing on Day 1 | 5.9 days |
| Part A SAD Cohort 4 AMG 133 | Part B: Tmax of AMG 133 | Total AMG 133 after dosing on Day 57 | 6.0 days |
| Part A SAD Cohort 4 AMG 133 | Part B: Tmax of AMG 133 | Total AMG 133 after dosing on Day 1 | 4.0 days |
| Part A SAD Cohort 4 AMG 133 | Part B: Tmax of AMG 133 | Intact AMG 133 after dosing on Day 1 | 4.0 days |
| Part A SAD Cohort 4 AMG 133 | Part B: Tmax of AMG 133 | Intact AMG 133 after dosing on Day 57 | 6.0 days |
Secondary
Percentage of Participants With Anti-AMG 133 Antibody Formation
The percentage of participants who developed anti-AMG 133 antibodies (binding and if positive, neutralizing to native GLP-1, when available) at any time was presented.
Time frame: Part A Cohort 1-6 and 11: Up to Day 150. Part B Cohort 7-10 and Part C Cohort 13: Up to Day 207. Part C Cohort 12: Up to Day 193
Population: Full analysis set: all randomized participants who received at least one dose of AMG 133 or placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A SAD Cohort 1 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Binding antibody positive | 16.7 percentage of participants |
| Part A SAD Cohort 1 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Neutralizing antibody positive | 0.0 percentage of participants |
| Part A SAD Cohort 2 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Binding antibody positive | 50.0 percentage of participants |
| Part A SAD Cohort 2 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Neutralizing antibody positive | 0.0 percentage of participants |
| Part A SAD Cohort 3 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Binding antibody positive | 28.6 percentage of participants |
| Part A SAD Cohort 3 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Neutralizing antibody positive | 0.0 percentage of participants |
| Part A SAD Cohort 4 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Binding antibody positive | 33.3 percentage of participants |
| Part A SAD Cohort 4 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Neutralizing antibody positive | 16.7 percentage of participants |
| Part A SAD Cohort 5 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Neutralizing antibody positive | 0.0 percentage of participants |
| Part A SAD Cohort 5 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Binding antibody positive | 16.7 percentage of participants |
| Part A SAD Cohort 6 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Neutralizing antibody positive | 0.0 percentage of participants |
| Part A SAD Cohort 6 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Binding antibody positive | 16.7 percentage of participants |
| Part A SAD Cohort 11 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Binding antibody positive | 0.0 percentage of participants |
| Part A SAD Cohort 11 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Neutralizing antibody positive | 0.0 percentage of participants |
| Part A SAD IV Placebo (Cohort 6) | Percentage of Participants With Anti-AMG 133 Antibody Formation | Binding antibody positive | 33.3 percentage of participants |
| Part A SAD IV Placebo (Cohort 6) | Percentage of Participants With Anti-AMG 133 Antibody Formation | Neutralizing antibody positive | 0.0 percentage of participants |
| Part B MAD Cohort 7 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Binding antibody positive | 25.0 percentage of participants |
| Part B MAD Cohort 7 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Neutralizing antibody positive | 0.0 percentage of participants |
| Part B MAD Cohort 8 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Neutralizing antibody positive | 0.0 percentage of participants |
| Part B MAD Cohort 8 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Binding antibody positive | 30.0 percentage of participants |
| Part B MAD Cohort 9 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Neutralizing antibody positive | 16.7 percentage of participants |
| Part B MAD Cohort 9 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Binding antibody positive | 33.3 percentage of participants |
| Part B MAD Cohort 10 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Binding antibody positive | 16.7 percentage of participants |
| Part B MAD Cohort 10 AMG 133 | Percentage of Participants With Anti-AMG 133 Antibody Formation | Neutralizing antibody positive | 0.0 percentage of participants |
| Part B MAD Cohorts 7-9 Placebo | Percentage of Participants With Anti-AMG 133 Antibody Formation | Neutralizing antibody positive | 0.0 percentage of participants |
| Part B MAD Cohorts 7-9 Placebo | Percentage of Participants With Anti-AMG 133 Antibody Formation | Binding antibody positive | 12.5 percentage of participants |