Obesity, Overweight or Obesity
Conditions
Keywords
Overweight, GLP-1
Brief summary
This study is designed to test how well MET097, an active drug, works to treat individuals with obesity or overweight when compared to placebo. MET097 or placebo will be given to individuals weekly for 28 weeks. If an individual is assigned to MET097 they will receive one of four different dose levels. Participants who have completed the first 28 weeks may participate in an exploratory extension study.
Detailed description
This is a multi-center, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of four different dose levels of MET097 vs. placebo for body weight loss in adult participants with obesity or overweight (body mass index \[BMI\] 27 to 50 kg/m2, aged 18 to 70), after 28 weeks with once weekly dosing. Participants who have completed the first 28 weeks may participate in an exploratory extension study that includes less frequent dosing regimens. After the dosing period, there is an additional post-treatment follow-up period.
Interventions
DRUGMET097
MET097 is an ultra-long-acting, fully-biased analog of human GLP-1.
DRUGPlacebo
Sterile 0.9% (w/v) saline will be used as placebo treatment during the study.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Body mass index (BMI) at Screening of: * BMI ≥30 kg/m2 and ≤50.0 kg/m2 (can have the weight-related co-morbidities listed below) * BMI ≥27.0 kg/m2 to \<30.0 kg/m2 with at least one of the following weight-related co-morbidities: 1. Hypertension: on blood pressure (BP)-lowering medication or having systolic BP ≥130 mmHg or diastolic BP ≥80 mmHg at Screening 2. Dyslipidemia: on lipid-lowering medication or having low-density lipoprotein cholesterol (LDL-C) ≥160 mg/dL (4.1 mmol/L) or triglycerides ≥150 mg/dL (1.7 mmol/L), or high-density lipoprotein-cholesterol (HDL-C) \<40 mg/dL (1.0 mmol/L) for men or HDL-C \<50 mg/dL (1.3 mmol/L) for women at Screening Stable body weight (increase or decrease ≤5 kg) within 3 months prior to Screening
Exclusion criteria
* Diagnosis of diabetes (T1DM or T2DM) or glycated hemoglobin A1c (HbA1c) ≥ 6.5% or fasting plasma glucose \>125 mg/dL. * Estimated glomerular filtration rate (eGFR) \<75 mL/min/1.73 m2 * History of pancreatitis * Family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2) * History of significant active or unstable major depressive disorder (MDD) or other severe psychiatric disorder within the last 2 years * Any lifetime history of a suicide attempt.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Weight at Week 28: Part A | Baseline (last non-missing measurement prior to the first dose), Week 28 | Analysis was performed using mixed model for repeated measures (MMRM) with treatment group, visit, and treatment by visit interaction, sex, and baseline body weight as fixed effects using unstructured covariance. The analysis excluded weight measurements after protocol specified intercurrent events (ICEs) including permanent treatment discontinuation, non-compliance to treatment and lifestyle change. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Weight at Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 106, 113, 141 and 169: Part A | Baseline, Day 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 106, 113, 141 and 169 | Analysis was performed using MMRM with treatment group, visit, and treatment by visit interaction, sex, and baseline body weight as fixed effects using unstructured covariance excluding weight measurements after protocol specified intercurrent ICEs. |
| Number of Participants With Reduction in Body Weight Greater Than or Equal to (>=) 5 Percent (%) From Baseline at Week 28: Part A | Baseline, Week 28 | — |
| Number of Participants With Reduction in Body Weight >= 10 % From Baseline at Week 28: Part A | Baseline, Week 28 | — |
| Number of Participants With Reduction in Body Weight >= 15 % From Baseline at Week 28: Part A | Baseline, Week 28 | — |
| Change From Baseline in Body Weight at Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 106, 113, 141, 169 and 197: Part A | Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 106, 113, 141, 169 and 197 | — |
| Change From Baseline in Body Mass Index (BMI) at Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 106, 113, 141, 169 and 197: Part A | Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 106, 113, 141, 169 and 197 | BMI was derived from body weight in kilograms (kg) and height in meters (m), and it was calculated as weight divided by height\^2. |
| Change From Baseline in Waist Circumference at Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 106, 113, 141, 169 and 197: Part A | Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 106, 113, 141, 169 and 197 | — |
| Number of Participants With Gastrointestinal (GI) Adverse Event of Clinical Interest (AECI): Part A | From Day 1 of dosing up to 28 days after last dose for Part A | An adverse event (AE) was defined as any untoward medical occurrence in a participant administered an investigational product and which did not necessarily have a causal relationship with the treatment. Gastrointestinal AECIs included nausea, vomiting and diarrhea. |
| Number of Participants With Treatment Related Gastrointestinal AECIs: Part A | From Day 1 of dosing up to 28 days after last dose for Part A | An AE was defined as any untoward medical occurrence in a participant administered an investigational product and which did not necessarily have a causal relationship with the treatment. Gastrointestinal AECIs included nausea, vomiting and diarrhea. Treatment related gastrointestinal AECIs were GI AECIs that were related to study drug and relatedness was judged by investigator. |
| Number of Participants With Gastrointestinal AECI and Treatment Related AECIs by Severity: Part A | From Day 1 of dosing up to 28 days after last dose for Part A | An AE was defined as any untoward medical occurrence in a participant administered an investigational product and which did not necessarily have a causal relationship with the treatment. Gastrointestinal AECIs included nausea, vomiting and diarrhea. Treatment related GI AECIs were GI AECIs that were related to study drug and relatedness was judged by investigator. Severity was assessed as mild: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; moderate: minimal, local or non-invasive intervention indicated, limiting age-appropriate instrumental activities of daily living and severe: medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self-care activities of daily living or life-threatening consequences, urgent intervention indicated or death related to an AE. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs: Part A | Up to Week 37 | An AE was defined as any untoward medical occurrence in a participant administered an investigational product and which does not necessarily have a causal relationship with the treatment. A TEAE was defined as any AE which on or after exposure to study treatment. Treatment related TEAEs were TEAEs that were related to study drug and relatedness was judged by investigator. |
| Number of Participants With TEAEs and Treatment-Related TEAEs by Severity: Part A | Up to Week 37 | An AE was defined as any untoward medical occurrence in participant administered an investigational product and which does not necessarily have causal relationship with treatment. A TEAE was defined as any AE which on or after exposure to study treatment up to 28 days following the last dose. Treatment related TEAEs were TEAEs that were related to study drug and relatedness was judged by investigator. Severity: mild: asymptomatic/ mild symptoms, clinical/ diagnostic observations only, intervention not indicated; moderate: minimal, local/ non-invasive intervention indicated, limiting age-appropriate instrumental activities of daily living and severe: medically significant but not immediately life-threatening, hospitalization/ prolongation of hospitalization indicated, disabling, limiting self-care activities of daily living/ life-threatening consequences, urgent intervention indicated/ death related to an AE. |
| Number of Participants With Abnormal Clinically Significant Physical Examination: Part A | From Day 1 of dosing up to post treatment follow up for Part A | The physical examination included examination of the following body systems (at minimum): head and neck (including complete thyroid exam), cardiovascular, respiratory, gastrointestinal, brief neurological, and general appearance. Clinical significance will be judged by investigator. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities: Part A | From Day 1 of dosing up to post treatment follow up for Part A | Twelve lead ECGs were measured with the participant in a supine position after at least 5 minutes. Clinical significance will be judged by investigator. |
| Number of Participants With Potential Clinically Significant Laboratory Values: Part A | From Day 1 of dosing up to post treatment follow up for Part A | Laboratory parameters assessed included alanine aminotransferase (ALT) (units per liter \[U/L\]): greater than (\>) 1\*upper limit of normal (ULN), \>3\*ULN and \>5\*ULN; alkaline phosphatase (ALP) (U/L): \>2\*ULN; amylase (U/L): \>1\*ULN and \>3\*ULN; aspartate aminotransferase (AST): \>1\*ULN, \>3\*ULN and \>5\*ULN; estimated glomerular filtration rate (eGFR) (Ckd-Epi \[chronic kidney disease epidemiology collaboration\]) (milliliter per minute per 1.73m\^2): less than (\<) 60 mL/min/1.73m\^2, 60-90 mL/min/1.73m\^2 and \>90 mL/min/1.73m\^2; Lipase: \>1\*ULN and \>3\*ULN; neutrophils: \<1.5, \<0.5, 0.5 to \<1, 1 to \<1.5 and total bilirubin (milligrams per deciliter): \>2\* upper limit of normal (ULN). Potential clinical significance was judged by investigator. |
| Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Categories: Part A | From Day 1 of dosing up to post treatment follow up for Part A | The C-SSRS is a questionnaire designed for the assessment of suicidal ideation and behavior in adolescents and adults. C-SSRS were evaluated through category 1 to 10. Suicidal ideation score was defined as the maximum suicidal ideation category (i.e., category 1-5), with 0 assigned if no ideation was present. Suicidal ideation, defined as 'Yes' if 'Yes' was present in any of category 1-5 and suicidal behavior, defined as 'Yes' if 'Yes' was present in any of category 6-10 and suicidal ideation or behavior, defined as 'Yes' if 'Yes' was present in any of Category 1-10. |
| Patient Health Questionnaire-9 (PHQ-9) Total Score: Part A | From Day 1 of dosing up to post treatment follow up for Part A | The PHQ-9 is a questionnaire designed to monitor and measure the severity of depression in participants. The questions included "little interest/pleasure in things", "feeling down depressed or hopeless", "trouble falling or staying asleep", "feeling tired or little energy", "poor appetite or overeating", "feeling bad about yourself", "trouble concentrating on things", "moving slowly or fidgety/restless" and "thoughts you be better off dead". Each item was scored on scale of "0=not at all", "several days", "more than half the days" to "nearly every day". The total score ranges from 0 to 27 by adding score for each question (total points) where: Score 1-4: minimal depression; Score 5-9: Mild depression; Score 10-14: moderate depression; Score 15-19 moderately severe depression; Score 20-27: Severe depression. Higher score indicates greater severity of depression. |
| Number of Participants With Anti Drug Antibodies (ADAs): Part A | From Day 1 of dosing up to post treatment follow up for Part A | Number of participants with baseline, positive and negative ADAs are reported in this outcome measure. |
| Minimum Observed Concentration (Cmin) of Berobenatide: Part A | From pre-dose on Day 1 up to 168 hours post-dose | — |
| Area Under the Concentration Versus Time Curve During the Dosing Interval (AUC[0-tau]) of Berobenatide: Part A | From pre-dose on Day 1 up to 168 hours post-dose | AUCtau was area under the concentration versus time curve during the dosing interval (tau), where, tau=168 hours. |
| Maximum Observed Concentration (Cmax) of Berobenatide: Part A | From pre-dose on Day 1 up to 168 hours post-dose | Cmax was observed directly from data. |
| Time to Maximum Concentration (Tmax) of Berobenatide: Part A | From pre-dose on Day 1 up to 168 hours post-dose | — |
| Plasma Concentration of Berobenatide: Part A | From pre-dose on Day 1 up to 168 hours post-dose | — |
| Percent Change From Baseline in Body Weight: Part B | Baseline (last available measurement prior to first dose received in Part A), End of study | — |
| Number of Participants With TEAEs: Part B | From Day 1 of dosing in Part B up to 28 days after last dose for Part B | An AE was defined as any untoward medical occurrence in a participant administered an investigational product and which does not necessarily have a causal relationship with the treatment. A TEAE was defined as any AE which on or after exposure to study treatment up to 28 days following the last dose. |
Countries
United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Recruitment details
The study consisted of 2 parts: Part A and optional Part B. Eligible participants who completed Week 28 (Day 197) assessments of Part A could enter Part B. The analysis for primary outcome measures are completed and results are reported based on primary analysis when all participants completed their Week 28 visit of Part A. Analysis for secondary outcome measures are still ongoing therefore, results for all secondary outcome measures and Part B of study will be reported upon study completion.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 40.3 Years STANDARD_DEVIATION 11.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 38 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 | 1 Participants |
| Race (NIH/OMB) White | 177 Participants |
| Sex: Female, Male Female | 151 Participants |
| Sex: Female, Male Male | 15 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 | 0 / 48 | 0 / 48 | 0 / 48 | 0 / 47 | 0 / 48 |
| other Total, other adverse events | 30 / 48 | 33 / 48 | 34 / 48 | 30 / 47 | 35 / 48 |
| serious Total, serious adverse events | 0 / 48 | 2 / 48 | 1 / 48 | 0 / 47 | 0 / 48 |
Outcome results
None listed