Trial Outcomes & Findings for Safety and Efficacy of Abaloparatide-SC in Men With Osteoporosis (ATOM) (NCT NCT03512262)

Results Overview

Lumbar Spine BMD was assessed by DXA scans evaluated by a central imaging laboratory. Lumbar spine scans included L1 through L4. Positive changes from baseline indicate improvement in bone health.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

228 participants

Primary outcome timeframe

Baseline, Month 12

Results posted on

2023-04-07

Participant Flow

Participants who remained eligible for study participation were randomly allocated, using a 2:1 randomization ratio (abaloparatide:placebo) on Day 1, to receive treatment with either blinded abaloparatide 80 micrograms (mcg) per day or daily placebo subcutaneous (SC) injections.

Participant milestones

Participant milestones
Measure	Abaloparatide Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Overall Study STARTED	149	79
Overall Study Received at Least 1 Dose of Study Drug	149	79
Overall Study COMPLETED	114	64
Overall Study NOT COMPLETED	35	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Abaloparatide Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Overall Study Adverse Event	8	3
Overall Study Death (non-treatment emergent)	1	0
Overall Study Withdrawal by Subject	17	9
Overall Study Lost to Follow-up	7	1
Overall Study Other than Specified	2	2

Baseline Characteristics

Safety and Efficacy of Abaloparatide-SC in Men With Osteoporosis (ATOM)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Abaloparatide n=149 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=79 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.	Total n=228 Participants Total of all reporting groups
Age, Continuous	68.5 years STANDARD_DEVIATION 8.25 • n=5 Participants	67.8 years STANDARD_DEVIATION 8.53 • n=7 Participants	68.3 years STANDARD_DEVIATION 8.34 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	149 Participants n=5 Participants	79 Participants n=7 Participants	228 Participants n=5 Participants
Race/Ethnicity, Customized Race: White	140 Participants n=5 Participants	76 Participants n=7 Participants	216 Participants n=5 Participants
Race/Ethnicity, Customized Race: Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race: Asian	8 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Race: Native Hawaiian or other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race: Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity: Hispanic or Latino	23 Participants n=5 Participants	13 Participants n=7 Participants	36 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity: Not Hispanic or Latino	124 Participants n=5 Participants	66 Participants n=7 Participants	190 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity: Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity: MIssing	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Lumbar Spine Bone Mineral Density (BMD) T-score	-2.11 BMD T-Score STANDARD_DEVIATION 1.119 • n=5 Participants	-2.05 BMD T-Score STANDARD_DEVIATION 1.217 • n=7 Participants	-2.09 BMD T-Score STANDARD_DEVIATION 1.152 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Month 12

Population: Intent-to-Treat (ITT) Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Lumbar Spine BMD was assessed by DXA scans evaluated by a central imaging laboratory. Lumbar spine scans included L1 through L4. Positive changes from baseline indicate improvement in bone health.

Outcome measures

Outcome measures
Measure	Abaloparatide n=119 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=66 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Percent Change From Baseline in Lumbar Spine BMD at Month 12	8.4820 percent change Standard Error 0.5353	1.1654 percent change Standard Error 0.7235

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Total hip BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health.

Outcome measures

Outcome measures
Measure	Abaloparatide n=119 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=66 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Percent Change From Baseline in Total Hip BMD at Month 12	2.1351 percent change Standard Error 0.2711	0.0143 percent change Standard Error 0.3543

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Femoral neck BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health.

Outcome measures

Outcome measures
Measure	Abaloparatide n=119 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=66 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Percent Change From Baseline in Femoral Neck BMD at Month 12	2.9766 percent change Standard Error 0.3448	0.1545 percent change Standard Error 0.4527

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Lumbar Spine BMD was assessed by DXA scans evaluated by a central imaging laboratory. Lumbar spine scans included L1 through L4. Positive changes from baseline indicate improvement in bone health.

Outcome measures

Outcome measures
Measure	Abaloparatide n=123 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=70 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Percent Change From Baseline in Lumbar Spine BMD at Month 6	5.5436 percent change Standard Error 0.4127	0.6418 percent change Standard Error 0.5472

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Total hip BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health.

Outcome measures

Outcome measures
Measure	Abaloparatide n=122 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=70 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Percent Change in Total Hip BMD From Baseline at Month 6	1.3888 percent change Standard Error 0.2142	0.0267 percent change Standard Error 0.2790

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Femoral neck BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health.

Outcome measures

Outcome measures
Measure	Abaloparatide n=122 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=70 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Percent Change From Baseline in Femoral Neck BMD at Month 6	1.4790 percent change Standard Error 0.2714	-0.1884 percent change Standard Error 0.3569

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Ultra-distal radius BMD was assessed by DXA scans. Positive changes from baseline indicate improvement in bone health.

Outcome measures

Outcome measures
Measure	Abaloparatide n=115 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=61 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Percent Change From Baseline in Ultra-Distal Radius BMD at Month 12	1.4358 percent change Standard Error 0.4236	-0.1915 percent change Standard Error 0.5722

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Distal one-third radius BMD was assessed by DXA scans. Positive changes from baseline indicate improvement in bone health.

Outcome measures

Outcome measures
Measure	Abaloparatide n=115 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=61 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Percent Change From Baseline in Distal One-third Radius BMD at Month 12	-0.0138 percent change Standard Error 0.3253	0.7066 percent change Standard Error 0.4285

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed is the total number of participants who had s-PINP evaluation at Baseline and Month 12.

Blood samples were taken to measure s-PINP, a bone formation marker. s-PINP concentrations reflect the rate of skeletal new bone formation. Increases in s-PINP indicate anabolic biologic response in the bone.

Outcome measures

Outcome measures
Measure	Abaloparatide n=119 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=65 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Percent Change From Baseline in Serum Procollagen Type I N-terminal Propeptide (s-PINP) at Month 12	225.919 percent change Standard Deviation 416.4173	0.291 percent change Standard Deviation 31.8038

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed is the total number of participants who had s-CTX evaluation at Baseline and Month 12.

Blood samples were taken to measure s-CTX. Elevated levels of s-CTX indicate increased bone resorption (bone loss).

Outcome measures

Outcome measures
Measure	Abaloparatide n=119 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=65 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Month 12	89.639 percent change Standard Deviation 206.7227	15.359 percent change Standard Deviation 40.3351

SECONDARY outcome

Timeframe: Baseline through Month 12

Population: ITT Population: All participants randomized into the study.

Radiological evaluations were performed to identify any new clinical fractures (occurring after the screening visit).

Outcome measures

Outcome measures
Measure	Abaloparatide n=149 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=79 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Number of Participants With New Clinical Fractures	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline through Month 12

Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed is the total number of participants who had baseline evaluation and also had end of treatment BMD disease category evaluation (normal, osteopenia, and osteoporosis). .

The percentage of participants converting from the categories of osteoporosis to osteopenia or from osteopenia to normal at End of Treatment (Month 12) was assessed. Osteoporosis was defined as lumbar spine or total hip BMD T-score ≤ -2.5. Osteopenia was defined as one of the following: * Lumbar spine \> -2.5 and total hip BMD T-score \> -2.5 and \< -1.0 * Lumbar spine \> -2.5 and \< -1.0 and total hip BMD T-score \> -2.5 * Normal was defined as lumbar spine and total hip BMD T-score ≥ -1.0.

Outcome measures

Outcome measures
Measure	Abaloparatide n=142 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=75 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Percent of Participants With Change in Disease Status Osteopenia to Normal	8.8 percentage of participants	8.0 percentage of participants
Percent of Participants With Change in Disease Status Osteopenia to Osteoporosis	0 percentage of participants	12.0 percentage of participants
Percent of Participants With Change in Disease Status Osteoporosis to Normal	2.9 percentage of participants	0 percentage of participants
Percent of Participants With Change in Disease Status Osteoporosis to Osteopenia	57.1 percentage of participants	12.8 percentage of participants
Percent of Participants With Change in Disease Status Normal to Osteopenia or Osteoporosis	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Month 12

Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Lumbar spine, femoral neck, and total hip BMD were assessed by DXA scans evaluated by a central imaging laboratory.

Outcome measures

Outcome measures
Measure	Abaloparatide n=119 Participants Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=66 Participants Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip BMD Increase >0% at All Three Sites	67.2 percentage of participants	15.2 percentage of participants
Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip BMD Increase >3% at All Three Sites	31.9 percentage of participants	1.5 percentage of participants
Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip BMD Increase >6% at All Three Sites	9.2 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Only 2 participants per reporting group had volumetric BMD measured by QCT at baseline and Month 12, therefore, no data is reported here to maintain participant confidentiality.

QCT scans were evaluated by a central imaging laboratory.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Only 2 participants per reporting group had volumetric BMD measured by QCT at baseline and Month 12, therefore, no data is reported here to maintain participant confidentiality.

QCT scans were evaluated by a central imaging laboratory.

Outcome measures

Outcome data not reported

Adverse Events

Abaloparatide

Serious events: 8 serious events

Other events: 73 other events

Deaths: 1 deaths

Placebo

Serious events: 4 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Abaloparatide n=149 participants at risk Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=79 participants at risk Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
General disorders Injection site erythema	12.8% 19/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	5.1% 4/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
General disorders Injection site swelling	6.7% 10/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	0.00% 0/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
General disorders Injection site pain	6.0% 9/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	0.00% 0/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Infections and infestations Nasopharyngitis	8.7% 13/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	7.6% 6/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Infections and infestations Bronchitis	5.4% 8/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	1.3% 1/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Infections and infestations Upper respiratory tract infection	4.7% 7/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	6.3% 5/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Infections and infestations Sinusitis	4.0% 6/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	5.1% 4/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Musculoskeletal and connective tissue disorders Arthralgia	6.7% 10/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	1.3% 1/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Musculoskeletal and connective tissue disorders Back pain	4.7% 7/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	6.3% 5/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Nervous system disorders Dizziness	8.7% 13/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	1.3% 1/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Nervous system disorders Headache	5.4% 8/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	5.1% 4/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Vascular disorders Hypertension	5.4% 8/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	5.1% 4/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.

Additional Information

Clinical Operations

Radius Health, Inc.

Phone: 617-551-4000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Abaloparatide n=149 participants at risk Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen.	Placebo n=79 participants at risk Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen.
Cardiac disorders Angina unstable	0.67% 1/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	0.00% 0/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Cardiac disorders Supraventricular tachycardia	0.67% 1/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	0.00% 0/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Cardiac disorders Acute myocardial infarction	0.00% 0/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	1.3% 1/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Cardiac disorders Mitral valve prolapse	0.00% 0/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	1.3% 1/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Gastrointestinal disorders Small intestinal obstruction	0.67% 1/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	0.00% 0/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Immune system disorders Skin graft rejection	0.00% 0/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	1.3% 1/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Infections and infestations Appendicitis	0.67% 1/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	0.00% 0/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Infections and infestations Influenza	0.67% 1/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	0.00% 0/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Injury, poisoning and procedural complications Burns third degree	0.00% 0/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	1.3% 1/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	1.3% 1/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.67% 1/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	0.00% 0/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Nervous system disorders Cerebrovascular accident	0.67% 1/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	0.00% 0/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Nervous system disorders Peripheral nerve palsy	0.67% 1/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	0.00% 0/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Injury, poisoning and procedural complications Toxicity to various agents	0.67% 1/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	0.00% 0/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.67% 1/149 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.	0.00% 0/79 • Day 1 (after dosing) through Month 13 Safety Population was used for analyses of treatment-emergent serious and "other" adverse events that occurred from Day 1 (after dosing) through Month 13. The one death recorded under "All-cause mortality" was due to an event that was not treatment-emergent.