Generalized Lipodystrophy
Conditions
Brief summary
The primary objectives of the study are to estimate the effects of REGN4461 on glycemic parameters in the subset of patients with elevated baseline hemoglobin A1c levels (HbA1c ≥7%) and to estimate the effects of REGN4461 on fasting triglyceride levels in the subset of patients with elevated baseline fasting triglycerides (TG ≥250 mg/dL). The secondary objectives are to estimate the effects of REGN4461 on a composite endpoint of changes in either HbA1c or fasting TG for all patients, estimate the effects of 3 dose levels of REGN4461 on glycemic parameters and fasting TG, to estimate the effects of REGN4461 on insulin sensitivity, to evaluate the safety and tolerability of REGN4461 and to evaluate the pharmacokinetics (PK) and immunogenicity of REGN4461.
Interventions
DRUGPlacebo
Intravenous (IV) infusion loading dose or subcutaneous (SC) injection weekly (QW).
DRUGLow-Dose REGN4461
IV infusion loading dose or SC injection QW.
DRUGHigh-dose REGN4461
IV infusion loading dose or SC injection QW.
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double Blind
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of congenital or acquired generalized lipodystrophy (GLD), as defined in the protocol * Presence of one or both of the following metabolic abnormalities at screening: 1. HbA1c ≥ 7% OR 2. Fasting TG ≥250 mg/dL * Generally stable diet (based on patient's recall) and medication regimen (that optimizes treatment for their metabolic disease) for at least 3 months prior to the screening visit Key
Exclusion criteria
* Treatment with metreleptin within 1 month of the screening visit * Treatment with over-the-counter or prescription medications for weight loss within 3 months prior to the screening visit * Treatment with oral glucocorticoids \>7.5 mg prednisone equivalents per day within 3 months prior to screening visit or plans to begin treatment with oral glucocorticoids \>7.5 mg prednisone equivalents per day during the study period * History of Human Immunodeficiency Virus (HIV) or HIV seropositivity at screening visit * Uncontrolled infection with hepatitis B or hepatitis C infection, or known active tuberculosis at screening * Participation in any clinical research study evaluating an Investigational product (IP) or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit. * Pregnant or breast-feeding women NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Participants With Elevated Baseline Hemoglobin A1c (HbA1c ≥7%) at Week 8 | Baseline, Week 8 | Absolute change from baseline in HbA1c for subgroup of participants with baseline HbA1c ≥7% reported |
| Absolute Change From Baseline in Fasting Glucose at Week 8 | Baseline, Week 8 | Absolute change from baseline in fasting glucose for subgroup of participants with baseline HbA1c ≥7% reported |
| Absolute Change From Baseline in Weighted Mean Glucose (WMG) at Week 8 | Baseline, Week 8 | Absolute change from baseline in WMG for subgroup of participants with baseline HbA1c ≥7% reported |
| Percent Change From Baseline in Fasting Triglycerides (TG) at Week 8 | Baseline, Week 8 | Percent change from baseline in participants with elevated baseline fasting TG (fasting TG ≥250 mg/dL) reported |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in HbA1c and Fasting TG Composite Endpoint at Week 8 | Baseline, Week 8 | The composite score is calculated for each individual participant using baseline and Week 8 measurements of HbA1c and fasting TG. For each participant, a Z-score is calculated separately for HbA1c and fasting TG, rescaling the change from baseline based on the standard deviation of the baseline value for all participants, as a way of standardizing the change value. The composite score uses one or both of the calculated Z-scores depending on which parameters were abnormal at baseline. If both, then the participant's composite is the average of the two parameter Z-scores. At the participant level, a Z-score of zero for either parameter indicates no change in that metabolic parameter, but a composite Z-score of zero can also reflect offsetting changes in metabolic parameters. A negative Z-score would be interpreted as an overall improvement in metabolic function, but a negative Z-score can also result from a decrease in one parameter not being canceled by an increase in the other. |
| Absolute Change From Baseline in Fasting Glucose | Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52 | — |
| Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52 | — |
| Percent Change From Baseline in Fasting TG | Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52 | — |
| Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52 | — |
| Absolute Change From Baseline in HbA1c | Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 12, 24, 52 | — |
| Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 12, 24, 52 | — |
| Absolute Change From Baseline in Weighted Mean Glucose (WMG) | Baseline, Weeks 16 and 24 | — |
| Absolute Change From Baseline in WMG for Participants With Baseline Fasting HbA1c ≥7% | Baseline, Weeks 16 and 24 | — |
| Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT) | Baseline, Weeks 8, 16, 24 | — |
| Change From Baseline in Glucose AUC0-4 During a MMTT for Participants With Baseline HbA1c ≥7% | Baseline, Weeks 8, 16, 24 | — |
| Change From Baseline in Glucose Infusion Rate Per Kilogram (kg) Body Mass During Hyperinsulinemia-euglycemic Clamp | Baseline, Weeks 8 and 52 | — |
| Change From Baseline in Glucose Infusion Rate Per kg Body Mass During Hyperinsulinemia-euglycemic Clamp for Participants With Baseline HbA1c ≥7% | Baseline, Weeks 8 and 52 | — |
| Change From Baseline in Glucose Clearance Rate (kITT) During Insulin-tolerance Test (ITT) | Baseline, Weeks 8 and 52 | — |
| Change From Baseline in Glucose kITT During ITT for Participants With Baseline HbA1c ≥7% | Baseline, Weeks 8 and 52 | — |
| Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | From first dose of DBTP study treatment through last dose of OLTP 5 study treatment plus 16 weeks (approximately 120 weeks) | — |
| Concentrations of Total REGN4461 in Serum Over Time | Weeks 0 (post-dose), 8, 16 (post-dose), 36, 52; OLTP 5 Weeks 4, 12, 24, 52 | — |
| Number of Participants With Anti-drug Antibodies (ADA) to REGN4461 | Approximately Week 128 | — |
Countries
Peru, Russia, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence A, DBTP 1-3 24-week double-blind treatment period (DBTP) comprised of 3 sequential 8-week DBTPs (1- 3). Participants progressed from DBTP 1 (day 1 to week 8) to DBTP 2 (weeks 8 to 16) to DBTP 3 (weeks 16 to 24). | 8 |
| Treatment Sequence B, DBTP 1 -3 24-week DBTP comprised of 3 sequential 8-week DBTPs (1- 3): DBTP 1 (day 1 to week 8) to DBTP 2 (weeks 8 to 16) to DBTP 3 (weeks 16 to 24). | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Treatment Sequence B, DBTP 1 -3 | Total | Treatment Sequence A, DBTP 1-3 |
|---|---|---|---|
| Age, Continuous | 30.3 Years STANDARD_DEVIATION 16.06 | 25.0 Years STANDARD_DEVIATION 12.7 | 19.8 Years STANDARD_DEVIATION 4.95 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 12 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Female | 8 Participants | 14 Participants | 6 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 2 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 6 / 8 | 7 / 8 | 6 / 8 | 7 / 8 | 5 / 8 | 6 / 8 | 8 / 8 | 7 / 8 | 5 / 6 | 3 / 4 |
| serious Total, serious adverse events | 1 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 1 / 8 | 1 / 8 | 1 / 8 | 3 / 8 | 1 / 6 | 1 / 4 |
Outcome results
Primary
Absolute Change From Baseline in Fasting Glucose at Week 8
Absolute change from baseline in fasting glucose for subgroup of participants with baseline HbA1c ≥7% reported
Time frame: Baseline, Week 8
Population: Glycemic analysis set (all randomized participants in only DBTP 1 who received any study drug and had elevated baseline HbA1c \[HbA1c ≥7%\])
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose at Week 8 | 15.5 milligrams per deciliter (mg/dL) | Standard Error 18.6 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose at Week 8 | 53.6 milligrams per deciliter (mg/dL) | Standard Error 19.9 |
95% CI: [-21.3, 97.5]
Primary
Absolute Change From Baseline in Participants With Elevated Baseline Hemoglobin A1c (HbA1c ≥7%) at Week 8
Absolute change from baseline in HbA1c for subgroup of participants with baseline HbA1c ≥7% reported
Time frame: Baseline, Week 8
Population: Glycemic analysis set (all randomized participants in only DBTP 1 who received any study drug and had elevated baseline HbA1c \[HbA1c ≥7%\])
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Participants With Elevated Baseline Hemoglobin A1c (HbA1c ≥7%) at Week 8 | -0.1 millimoles per mole (mmol/mol) | Standard Error 0.6 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Participants With Elevated Baseline Hemoglobin A1c (HbA1c ≥7%) at Week 8 | 0.2 millimoles per mole (mmol/mol) | Standard Error 0.7 |
95% CI: [-1.9, 2.3]
Primary
Absolute Change From Baseline in Weighted Mean Glucose (WMG) at Week 8
Absolute change from baseline in WMG for subgroup of participants with baseline HbA1c ≥7% reported
Time frame: Baseline, Week 8
Population: Glycemic analysis set (all randomized participants in only DBTP 1 who received any study drug and had elevated baseline HbA1c \[HbA1c ≥7%\])
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Weighted Mean Glucose (WMG) at Week 8 | -3.7 mg/dL | Standard Error 19.9 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Weighted Mean Glucose (WMG) at Week 8 | -3.7 mg/dL | Standard Error 23.4 |
95% CI: [-56.9, 56.9]
Primary
Percent Change From Baseline in Fasting Triglycerides (TG) at Week 8
Percent change from baseline in participants with elevated baseline fasting TG (fasting TG ≥250 mg/dL) reported
Time frame: Baseline, Week 8
Population: Triglyceride analysis set (all randomized participants in only DBTP 1 who received any study drug and had elevated baseline fasting TG (TG ≥250 mg/dL)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 8 | -6.0 percentage of change | Standard Error 29.8 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 8 | 11.8 percentage of change | Standard Error 29.8 |
95% CI: [-67.6, 103.2]
Secondary
Absolute Change From Baseline in Fasting Glucose
Time frame: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose | Week 24 | -68.8 mg/dL | Standard Deviation 58.74 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose | Week 36 | -47.6 mg/dL | Standard Deviation 71.04 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose | Week 52 | -55.1 mg/dL | Standard Deviation 77.97 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose | OLTP 5 Week 4 | -91.8 mg/dL | Standard Deviation 61.29 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose | Week 16 | -29.4 mg/dL | Standard Deviation 59.8 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose | OLTP 5 Week 12 | -82.9 mg/dL | Standard Deviation 63.16 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose | OLTP 5 Week 24 | -100.5 mg/dL | Standard Deviation 55.15 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose | OLTP 5 Week 52 | -91.0 mg/dL | Standard Deviation 84.38 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose | OLTP 5 Week 52 | -111.2 mg/dL | Standard Deviation 125.57 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose | Week 24 | -21.1 mg/dL | Standard Deviation 82.85 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose | OLTP 5 Week 12 | -119.9 mg/dL | Standard Deviation 64.64 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose | Week 36 | 12.5 mg/dL | Standard Deviation 119.63 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose | Week 16 | -22.0 mg/dL | Standard Deviation 47.85 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose | Week 52 | 6.9 mg/dL | Standard Deviation 68.64 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose | OLTP 5 Week 24 | -40.7 mg/dL | Standard Deviation 110.2 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose | OLTP 5 Week 4 | -39.8 mg/dL | Standard Deviation 45.36 |
Secondary
Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7%
Time frame: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | Week 16 | -29.4 mg/dL | Standard Deviation 59.8 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | Week 24 | -68.8 mg/dL | Standard Deviation 58.74 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | Week 36 | -47.6 mg/dL | Standard Deviation 71.04 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | Week 52 | -55.1 mg/dL | Standard Deviation 77.97 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 4 | -91.8 mg/dL | Standard Deviation 61.29 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 12 | -82.9 mg/dL | Standard Deviation 63.16 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 24 | -100.5 mg/dL | Standard Deviation 55.15 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 52 | -91.0 mg/dL | Standard Deviation 84.38 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 52 | -111.2 mg/dL | Standard Deviation 125.57 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | Week 16 | -26.3 mg/dL | Standard Deviation 50.89 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 4 | -39.8 mg/dL | Standard Deviation 45.36 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | Week 24 | -24.5 mg/dL | Standard Deviation 90.23 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 24 | -40.7 mg/dL | Standard Deviation 110.2 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | Week 36 | 13.1 mg/dL | Standard Deviation 129.2 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 12 | -119.9 mg/dL | Standard Deviation 64.64 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% | Week 52 | 8.2 mg/dL | Standard Deviation 75.1 |
Secondary
Absolute Change From Baseline in HbA1c
Time frame: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 12, 24, 52
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c | Week 16 | -0.60 Percentage of HbA1c | Standard Deviation 2.2 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c | Week 36 | -2.56 Percentage of HbA1c | Standard Deviation 1.985 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c | OLTP 5 Week 24 | -3.32 Percentage of HbA1c | Standard Deviation 2.294 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c | Week 52 | -2.69 Percentage of HbA1c | Standard Deviation 2.12 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c | Week 24 | -2.34 Percentage of HbA1c | Standard Deviation 1.897 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c | OLTP 5 Week 52 | -1.67 Percentage of HbA1c | Standard Deviation 3.066 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c | OLTP 5 Week 12 | -3.57 Percentage of HbA1c | Standard Deviation 1.957 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c | OLTP 5 Week 52 | -3.30 Percentage of HbA1c | Standard Deviation 2.821 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c | OLTP 5 Week 12 | -1.53 Percentage of HbA1c | Standard Deviation 2.472 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c | OLTP 5 Week 24 | -1.45 Percentage of HbA1c | Standard Deviation 2.716 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c | Week 16 | -0.50 Percentage of HbA1c | Standard Deviation 1.664 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c | Week 24 | -0.85 Percentage of HbA1c | Standard Deviation 1.998 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c | Week 36 | -0.83 Percentage of HbA1c | Standard Deviation 2.147 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c | Week 52 | -1.59 Percentage of HbA1c | Standard Deviation 2.338 |
Secondary
Absolute Change From Baseline in HbA1c and Fasting TG Composite Endpoint at Week 8
The composite score is calculated for each individual participant using baseline and Week 8 measurements of HbA1c and fasting TG. For each participant, a Z-score is calculated separately for HbA1c and fasting TG, rescaling the change from baseline based on the standard deviation of the baseline value for all participants, as a way of standardizing the change value. The composite score uses one or both of the calculated Z-scores depending on which parameters were abnormal at baseline. If both, then the participant's composite is the average of the two parameter Z-scores. At the participant level, a Z-score of zero for either parameter indicates no change in that metabolic parameter, but a composite Z-score of zero can also reflect offsetting changes in metabolic parameters. A negative Z-score would be interpreted as an overall improvement in metabolic function, but a negative Z-score can also result from a decrease in one parameter not being canceled by an increase in the other.
Time frame: Baseline, Week 8
Population: Subgroup of participants with baseline HbA1c ≥ 7% or TG ≥ 250 mg/dL
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c and Fasting TG Composite Endpoint at Week 8 | 0.0 Z-score | Standard Error 0.2 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c and Fasting TG Composite Endpoint at Week 8 | 0.1 Z-score | Standard Error 0.3 |
Secondary
Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7%
Time frame: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 12, 24, 52
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | Week 36 | -2.56 Percentage of HbA1c | Standard Deviation 1.985 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 12 | -3.57 Percentage of HbA1c | Standard Deviation 1.957 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | Week 24 | -2.34 Percentage of HbA1c | Standard Deviation 1.897 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 24 | -3.32 Percentage of HbA1c | Standard Deviation 2.294 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | Week 52 | -2.69 Percentage of HbA1c | Standard Deviation 2.12 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 52 | -1.67 Percentage of HbA1c | Standard Deviation 3.066 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | Week 16 | -0.60 Percentage of HbA1c | Standard Deviation 2.2 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 52 | -3.30 Percentage of HbA1c | Standard Deviation 2.821 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | Week 16 | -0.36 Percentage of HbA1c | Standard Deviation 1.82 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | Week 24 | -0.77 Percentage of HbA1c | Standard Deviation 2.145 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | Week 36 | -0.74 Percentage of HbA1c | Standard Deviation 2.305 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | Week 52 | -1.65 Percentage of HbA1c | Standard Deviation 2.554 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 12 | -1.53 Percentage of HbA1c | Standard Deviation 2.472 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% | OLTP 5 Week 24 | -1.45 Percentage of HbA1c | Standard Deviation 2.716 |
Secondary
Absolute Change From Baseline in Weighted Mean Glucose (WMG)
Time frame: Baseline, Weeks 16 and 24
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Weighted Mean Glucose (WMG) | Week 16 | -10.626 mg/dL | Standard Deviation 28.6416 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in Weighted Mean Glucose (WMG) | Week 24 | -73.634 mg/dL | Standard Deviation 67.7436 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Weighted Mean Glucose (WMG) | Week 24 | -49.107 mg/dL | Standard Deviation 85.0349 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in Weighted Mean Glucose (WMG) | Week 16 | -7.579 mg/dL | Standard Deviation 96.4257 |
Secondary
Absolute Change From Baseline in WMG for Participants With Baseline Fasting HbA1c ≥7%
Time frame: Baseline, Weeks 16 and 24
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in WMG for Participants With Baseline Fasting HbA1c ≥7% | Week 16 | -10.626 mg/dL | Standard Deviation 28.6416 |
| Treatment Sequence A: DBTP 1: | Absolute Change From Baseline in WMG for Participants With Baseline Fasting HbA1c ≥7% | Week 24 | -73.634 mg/dL | Standard Deviation 67.7436 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in WMG for Participants With Baseline Fasting HbA1c ≥7% | Week 16 | -4.510 mg/dL | Standard Deviation 111.0606 |
| Treatment Sequence B: DBTP 1 | Absolute Change From Baseline in WMG for Participants With Baseline Fasting HbA1c ≥7% | Week 24 | -53.797 mg/dL | Standard Deviation 92.1541 |
Secondary
Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT)
Time frame: Baseline, Weeks 8, 16, 24
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT) | Week 8 | 829.3 mg/dL*minutes | Standard Deviation 12465.83 |
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT) | Week 16 | -5300.7 mg/dL*minutes | Standard Deviation 12605.15 |
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT) | Week 24 | -18000.6 mg/dL*minutes | Standard Deviation 14760.99 |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT) | Week 8 | 1479.3 mg/dL*minutes | Standard Deviation 6075.13 |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT) | Week 16 | 3734.1 mg/dL*minutes | Standard Deviation 22343.37 |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT) | Week 24 | -5777.7 mg/dL*minutes | Standard Deviation 14328.54 |
Secondary
Change From Baseline in Glucose AUC0-4 During a MMTT for Participants With Baseline HbA1c ≥7%
Time frame: Baseline, Weeks 8, 16, 24
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose AUC0-4 During a MMTT for Participants With Baseline HbA1c ≥7% | Week 8 | 829.3 mg/dL*minutes | Standard Deviation 12465.83 |
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose AUC0-4 During a MMTT for Participants With Baseline HbA1c ≥7% | Week 16 | -5300.7 mg/dL*minutes | Standard Deviation 12605.15 |
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose AUC0-4 During a MMTT for Participants With Baseline HbA1c ≥7% | Week 24 | -18000.6 mg/dL*minutes | Standard Deviation 14760.99 |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose AUC0-4 During a MMTT for Participants With Baseline HbA1c ≥7% | Week 8 | 3098.2 mg/dL*minutes | Standard Deviation 5145.73 |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose AUC0-4 During a MMTT for Participants With Baseline HbA1c ≥7% | Week 16 | 5976.4 mg/dL*minutes | Standard Deviation 25141.92 |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose AUC0-4 During a MMTT for Participants With Baseline HbA1c ≥7% | Week 24 | -5828.2 mg/dL*minutes | Standard Deviation 15695.44 |
Secondary
Change From Baseline in Glucose Clearance Rate (kITT) During Insulin-tolerance Test (ITT)
Time frame: Baseline, Weeks 8 and 52
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose Clearance Rate (kITT) During Insulin-tolerance Test (ITT) | Week 8 | 0.021 %mg/dL/min | — |
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose Clearance Rate (kITT) During Insulin-tolerance Test (ITT) | Week 52 | 2.311 %mg/dL/min | Standard Deviation 0.1712 |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose Clearance Rate (kITT) During Insulin-tolerance Test (ITT) | Week 8 | 2.230 %mg/dL/min | Standard Deviation 2.4771 |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose Clearance Rate (kITT) During Insulin-tolerance Test (ITT) | Week 52 | 0.632 %mg/dL/min | Standard Deviation 0.2064 |
Secondary
Change From Baseline in Glucose Infusion Rate Per kg Body Mass During Hyperinsulinemia-euglycemic Clamp for Participants With Baseline HbA1c ≥7%
Time frame: Baseline, Weeks 8 and 52
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose Infusion Rate Per kg Body Mass During Hyperinsulinemia-euglycemic Clamp for Participants With Baseline HbA1c ≥7% | Week 8 | 0.030 mg/kg/min | Standard Deviation 0.4224 |
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose Infusion Rate Per kg Body Mass During Hyperinsulinemia-euglycemic Clamp for Participants With Baseline HbA1c ≥7% | Week 52 | 6.256 mg/kg/min | — |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose Infusion Rate Per kg Body Mass During Hyperinsulinemia-euglycemic Clamp for Participants With Baseline HbA1c ≥7% | Week 8 | 0.572 mg/kg/min | Standard Deviation 1.4186 |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose Infusion Rate Per kg Body Mass During Hyperinsulinemia-euglycemic Clamp for Participants With Baseline HbA1c ≥7% | Week 52 | 3.740 mg/kg/min | Standard Deviation 2.8121 |
Secondary
Change From Baseline in Glucose Infusion Rate Per Kilogram (kg) Body Mass During Hyperinsulinemia-euglycemic Clamp
Time frame: Baseline, Weeks 8 and 52
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose Infusion Rate Per Kilogram (kg) Body Mass During Hyperinsulinemia-euglycemic Clamp | Week 8 | 0.030 mg/kg/min | Standard Deviation 0.4224 |
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose Infusion Rate Per Kilogram (kg) Body Mass During Hyperinsulinemia-euglycemic Clamp | Week 52 | 6.256 mg/kg/min | — |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose Infusion Rate Per Kilogram (kg) Body Mass During Hyperinsulinemia-euglycemic Clamp | Week 8 | 4.789 mg/kg/min | Standard Deviation 7.3736 |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose Infusion Rate Per Kilogram (kg) Body Mass During Hyperinsulinemia-euglycemic Clamp | Week 52 | 4.776 mg/kg/min | Standard Deviation 3.0924 |
Secondary
Change From Baseline in Glucose kITT During ITT for Participants With Baseline HbA1c ≥7%
Time frame: Baseline, Weeks 8 and 52
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose kITT During ITT for Participants With Baseline HbA1c ≥7% | Week 8 | 0.021 %mg/dL/min | — |
| Treatment Sequence A: DBTP 1: | Change From Baseline in Glucose kITT During ITT for Participants With Baseline HbA1c ≥7% | Week 52 | 2.311 %mg/dL/min | Standard Deviation 0.1712 |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose kITT During ITT for Participants With Baseline HbA1c ≥7% | Week 8 | 2.230 %mg/dL/min | Standard Deviation 2.4771 |
| Treatment Sequence B: DBTP 1 | Change From Baseline in Glucose kITT During ITT for Participants With Baseline HbA1c ≥7% | Week 52 | 0.632 %mg/dL/min | Standard Deviation 0.2064 |
Secondary
Concentrations of Total REGN4461 in Serum Over Time
Time frame: Weeks 0 (post-dose), 8, 16 (post-dose), 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Concentrations of Total REGN4461 in Serum Over Time | Week 8 | 45.8 mg/L | Standard Deviation 6.82 |
| Treatment Sequence A: DBTP 1: | Concentrations of Total REGN4461 in Serum Over Time | OLTP 5 Week 4 | 167 mg/L | Standard Deviation 72.2 |
| Treatment Sequence A: DBTP 1: | Concentrations of Total REGN4461 in Serum Over Time | Week 36 | 54.3 mg/L | Standard Deviation 36.4 |
| Treatment Sequence A: DBTP 1: | Concentrations of Total REGN4461 in Serum Over Time | OLTP5 Week 12 | 185 mg/L | Standard Deviation 67.2 |
| Treatment Sequence A: DBTP 1: | Concentrations of Total REGN4461 in Serum Over Time | Week 16 (post-dose) | 2.34 mg/L | Standard Deviation 3.44 |
| Treatment Sequence A: DBTP 1: | Concentrations of Total REGN4461 in Serum Over Time | OLTP5 Week 36 | 156 mg/L | Standard Deviation 77 |
| Treatment Sequence A: DBTP 1: | Concentrations of Total REGN4461 in Serum Over Time | Week 52 | 60.1 mg/L | Standard Deviation 45.1 |
| Treatment Sequence A: DBTP 1: | Concentrations of Total REGN4461 in Serum Over Time | OLTP5 Week 52 | 196 mg/L | Standard Deviation 106 |
| Treatment Sequence A: DBTP 1: | Concentrations of Total REGN4461 in Serum Over Time | Week 0 (post-dose) | 0 mg/L | Standard Deviation 0 |
| Treatment Sequence B: DBTP 1 | Concentrations of Total REGN4461 in Serum Over Time | OLTP5 Week 52 | 378 mg/L | Standard Deviation 224 |
| Treatment Sequence B: DBTP 1 | Concentrations of Total REGN4461 in Serum Over Time | Week 0 (post-dose) | 49.2 mg/L | Standard Deviation 13.8 |
| Treatment Sequence B: DBTP 1 | Concentrations of Total REGN4461 in Serum Over Time | Week 8 | 2.51 mg/L | Standard Deviation 3.11 |
| Treatment Sequence B: DBTP 1 | Concentrations of Total REGN4461 in Serum Over Time | Week 16 (post-dose) | 50.6 mg/L | Standard Deviation 38.7 |
| Treatment Sequence B: DBTP 1 | Concentrations of Total REGN4461 in Serum Over Time | Week 36 | 67.7 mg/L | Standard Deviation 44.2 |
| Treatment Sequence B: DBTP 1 | Concentrations of Total REGN4461 in Serum Over Time | Week 52 | 68.8 mg/L | Standard Deviation 41.2 |
| Treatment Sequence B: DBTP 1 | Concentrations of Total REGN4461 in Serum Over Time | OLTP 5 Week 4 | 167 mg/L | Standard Deviation 60.6 |
| Treatment Sequence B: DBTP 1 | Concentrations of Total REGN4461 in Serum Over Time | OLTP5 Week 12 | 194 mg/L | Standard Deviation 80.6 |
| Treatment Sequence B: DBTP 1 | Concentrations of Total REGN4461 in Serum Over Time | OLTP5 Week 36 | 355 mg/L | Standard Deviation 166 |
Secondary
Number of Participants With Anti-drug Antibodies (ADA) to REGN4461
Time frame: Approximately Week 128
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Sequence A: DBTP 1: | Number of Participants With Anti-drug Antibodies (ADA) to REGN4461 | 0 Participants |
| Treatment Sequence B: DBTP 1 | Number of Participants With Anti-drug Antibodies (ADA) to REGN4461 | 0 Participants |
Secondary
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)
Time frame: From first dose of DBTP study treatment through last dose of OLTP 5 study treatment plus 16 weeks (approximately 120 weeks)
Population: Double-blind Safety Analysis Set (DBTP SAF): Randomized participants who received any double-blind study drug; OLTP safety analysis set for Period 4 (OLTP 4 SAF): Randomized participants who received any open-label treatment period 4 study drug; OLTP 5 SAF: Randomized participants who received any open-label treatment period 5 study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | DBTP 1-3 | 7 Participants |
| Treatment Sequence A: DBTP 1: | Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | OLTP 4 | 8 Participants |
| Treatment Sequence A: DBTP 1: | Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | OLTP 5 | 1 Participants |
| Treatment Sequence B: DBTP 1 | Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | DBTP 1-3 | 8 Participants |
| Treatment Sequence B: DBTP 1 | Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | OLTP 4 | 7 Participants |
| Treatment Sequence B: DBTP 1 | Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | OLTP 5 | 6 Participants |
Secondary
Percent Change From Baseline in Fasting TG
Time frame: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG | Week 16 | -22.5 Percentage of change | Standard Deviation 48.21 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG | Week 24 | -55.1 Percentage of change | Standard Deviation 30.6 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG | Week 36 | -40.2 Percentage of change | Standard Deviation 39.19 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG | Week 52 | -9.7 Percentage of change | Standard Deviation 74.05 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG | OLTP 5 Week 4 | -71.5 Percentage of change | Standard Deviation 18.79 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG | OLTP 5 Week 12 | -56.0 Percentage of change | Standard Deviation 38.07 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG | OLTP 5 Week 24 | -64.4 Percentage of change | Standard Deviation 29.59 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG | OLTP 5 Week 52 | -77.4 Percentage of change | Standard Deviation 13.37 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG | OLTP 5 Week 52 | -85.8 Percentage of change | Standard Deviation 11.89 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG | Week 16 | -50.2 Percentage of change | Standard Deviation 39.99 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG | OLTP 5 Week 4 | -58.2 Percentage of change | Standard Deviation 21.6 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG | Week 24 | -45.7 Percentage of change | Standard Deviation 44.61 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG | OLTP 5 Week 24 | -67.4 Percentage of change | Standard Deviation 22.32 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG | Week 36 | -43.9 Percentage of change | Standard Deviation 51.07 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG | OLTP 5 Week 12 | -80.0 Percentage of change | Standard Deviation 17.52 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG | Week 52 | -60.3 Percentage of change | Standard Deviation 20.38 |
Secondary
Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL
Time frame: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Population: Number Analyzed equals number of participants analyzed at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | Week 16 | -39.4 Percentage of change | Standard Deviation 36.26 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | Week 24 | -62.8 Percentage of change | Standard Deviation 30.8 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | Week 36 | -48.6 Percentage of change | Standard Deviation 41.67 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | Week 52 | 0.7 Percentage of change | Standard Deviation 85.36 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | OLTP 5 Week 4 | -72.2 Percentage of change | Standard Deviation 20.92 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | OLTP 5 Week 12 | -54.9 Percentage of change | Standard Deviation 42.46 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | OLTP 5 Weeks 24 | -64.0 Percentage of change | Standard Deviation 33.06 |
| Treatment Sequence A: DBTP 1: | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | OLTP 5 Week 52 | -77.4 Percentage of change | Standard Deviation 13.37 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | OLTP 5 Week 52 | -85.8 Percentage of change | Standard Deviation 11.89 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | Week 16 | -45.4 Percentage of change | Standard Deviation 47.97 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | OLTP 5 Week 4 | -58.2 Percentage of change | Standard Deviation 21.6 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | Week 24 | -42.4 Percentage of change | Standard Deviation 53.75 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | OLTP 5 Weeks 24 | -67.4 Percentage of change | Standard Deviation 22.32 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | Week 36 | -44.0 Percentage of change | Standard Deviation 60.31 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | OLTP 5 Week 12 | -80.0 Percentage of change | Standard Deviation 17.52 |
| Treatment Sequence B: DBTP 1 | Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL | Week 52 | -63.4 Percentage of change | Standard Deviation 22.22 |