Trial Outcomes & Findings for A Phase II/III, Double-blind, Parallel Group Comparative Study of Oral Administration of NE-58095 Tablets (NCT NCT02063854)

NCT ID: NCT02063854

Last Updated: 2017-02-23

Results Overview

The change in BMD in the second to the fourth lumbar vertebrae, L2 to L4, and the averages of L2 to L4 at end of study relative to baseline. DXA is a means of measuring BMD through x-ray.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

871 participants

Primary outcome timeframe

Baseline and End of Study (up to Month 12)

Results posted on

2017-02-23

Participant Flow

Participants took part in the study at 67 investigative sites in Japan from 21 February 2014 to 19 November 2015.

Participants with a diagnosis of involutional osteoporosis were randomized at a ratio of 3:1:3:1:1:3:1 into 1 of 7 treatment groups: once-daily NE-58095 2.5 mg immediate release (IR) or once-monthly NE-58095 25 mg or 37.5 mg delayed release (DR) on awakening, after breakfast or 30 minutes following breakfast.

Participant milestones

Participant milestones
Measure	NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Overall Study STARTED	199	66	206	68	65	201	66
Overall Study Full Analysis Set: Received Study Drug	199	66	206	68	65	200	66
Overall Study COMPLETED	178	54	176	58	54	170	60
Overall Study NOT COMPLETED	21	12	30	10	11	31	6

Reasons for withdrawal

Reasons for withdrawal
Measure	NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Overall Study Pretreatment Event/Adverse Event	13	10	13	8	7	18	4
Overall Study Major Protocol Deviation	0	0	3	0	0	0	0
Overall Study Voluntary Withdrawal	2	0	8	1	3	6	1
Overall Study Surgical Dental Work Performed/Planned	5	2	6	1	1	6	1
Overall Study Reason Not Specified	1	0	0	0	0	0	0
Overall Study Did Not Receive Study Drug	0	0	0	0	0	1	0

Baseline Characteristics

A Phase II/III, Double-blind, Parallel Group Comparative Study of Oral Administration of NE-58095 Tablets

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NE-58095 DR 37.5 mg Once Monthly on Awakening n=65 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly Following Breakfast n=201 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast n=66 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	Total n=871 Participants Total of all reporting groups	NE-58095 IR 2.5 mg Once Daily on Awakening n=199 Participants NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly on Awakening n=66 Participants NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly Following Breakfast n=206 Participants NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast n=68 Participants NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Age, Continuous	69.0 years STANDARD_DEVIATION 6.98 • n=21 Participants	69.6 years STANDARD_DEVIATION 7.19 • n=8 Participants	69.8 years STANDARD_DEVIATION 7.87 • n=8 Participants	68.9 years STANDARD_DEVIATION 7.45 • n=24 Participants	68.9 years STANDARD_DEVIATION 7.32 • n=5 Participants	69.0 years STANDARD_DEVIATION 8.18 • n=7 Participants	68.2 years STANDARD_DEVIATION 7.68 • n=5 Participants	68.4 years STANDARD_DEVIATION 7.24 • n=4 Participants
Sex: Female, Male Female	63 Participants n=21 Participants	198 Participants n=8 Participants	63 Participants n=8 Participants	847 Participants n=24 Participants	190 Participants n=5 Participants	64 Participants n=7 Participants	203 Participants n=5 Participants	66 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=21 Participants	3 Participants n=8 Participants	3 Participants n=8 Participants	24 Participants n=24 Participants	9 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment Japan	65 participants n=21 Participants	201 participants n=8 Participants	66 participants n=8 Participants	871 participants n=24 Participants	199 participants n=5 Participants	66 participants n=7 Participants	206 participants n=5 Participants	68 participants n=4 Participants
Height	153.5 cm STANDARD_DEVIATION 5.13 • n=21 Participants	151.3 cm STANDARD_DEVIATION 5.20 • n=8 Participants	151.9 cm STANDARD_DEVIATION 6.47 • n=8 Participants	151.9 cm STANDARD_DEVIATION 6.00 • n=24 Participants	152.1 cm STANDARD_DEVIATION 6.59 • n=5 Participants	151.0 cm STANDARD_DEVIATION 6.64 • n=7 Participants	151.9 cm STANDARD_DEVIATION 6.11 • n=5 Participants	152.5 cm STANDARD_DEVIATION 5.49 • n=4 Participants
Weight	51.26 kg STANDARD_DEVIATION 7.473 • n=21 Participants	50.36 kg STANDARD_DEVIATION 7.383 • n=8 Participants	50.51 kg STANDARD_DEVIATION 7.427 • n=8 Participants	50.46 kg STANDARD_DEVIATION 7.544 • n=24 Participants	50.52 kg STANDARD_DEVIATION 7.975 • n=5 Participants	49.98 kg STANDARD_DEVIATION 6.720 • n=7 Participants	50.20 kg STANDARD_DEVIATION 7.231 • n=5 Participants	50.97 kg STANDARD_DEVIATION 8.736 • n=4 Participants
Body Mass Index (BMI)	21.79 kg/m^2 STANDARD_DEVIATION 3.289 • n=21 Participants	22.00 kg/m^2 STANDARD_DEVIATION 3.105 • n=8 Participants	21.90 kg/m^2 STANDARD_DEVIATION 3.071 • n=8 Participants	21.87 kg/m^2 STANDARD_DEVIATION 3.092 • n=24 Participants	21.82 kg/m^2 STANDARD_DEVIATION 3.009 • n=5 Participants	21.93 kg/m^2 STANDARD_DEVIATION 2.830 • n=7 Participants	21.75 kg/m^2 STANDARD_DEVIATION 2.926 • n=5 Participants	21.97 kg/m^2 STANDARD_DEVIATION 3.875 • n=4 Participants
Smoking Classification Never smoked	54 participants n=21 Participants	168 participants n=8 Participants	58 participants n=8 Participants	733 participants n=24 Participants	167 participants n=5 Participants	55 participants n=7 Participants	178 participants n=5 Participants	53 participants n=4 Participants
Smoking Classification Current smoker	3 participants n=21 Participants	7 participants n=8 Participants	3 participants n=8 Participants	41 participants n=24 Participants	10 participants n=5 Participants	4 participants n=7 Participants	11 participants n=5 Participants	3 participants n=4 Participants
Smoking Classification Ex-smoker	8 participants n=21 Participants	26 participants n=8 Participants	5 participants n=8 Participants	97 participants n=24 Participants	22 participants n=5 Participants	7 participants n=7 Participants	17 participants n=5 Participants	12 participants n=4 Participants
Menopausal Status Natural Menopause	53 participants n=21 Participants	180 participants n=8 Participants	59 participants n=8 Participants	759 participants n=24 Participants	170 participants n=5 Participants	58 participants n=7 Participants	179 participants n=5 Participants	60 participants n=4 Participants
Menopausal Status Artificial Menopause	10 participants n=21 Participants	18 participants n=8 Participants	4 participants n=8 Participants	88 participants n=24 Participants	20 participants n=5 Participants	6 participants n=7 Participants	24 participants n=5 Participants	6 participants n=4 Participants
Number of Years After Menopause, Categorical Min - ≤5 years	3 participants n=21 Participants	4 participants n=8 Participants	2 participants n=8 Participants	31 participants n=24 Participants	6 participants n=5 Participants	5 participants n=7 Participants	7 participants n=5 Participants	4 participants n=4 Participants
Number of Years After Menopause, Categorical 6 - ≤10 years	8 participants n=21 Participants	22 participants n=8 Participants	6 participants n=8 Participants	92 participants n=24 Participants	23 participants n=5 Participants	1 participants n=7 Participants	28 participants n=5 Participants	4 participants n=4 Participants
Number of Years After Menopause, Categorical 11 - ≤20 years	20 participants n=21 Participants	61 participants n=8 Participants	20 participants n=8 Participants	281 participants n=24 Participants	59 participants n=5 Participants	21 participants n=7 Participants	71 participants n=5 Participants	29 participants n=4 Participants
Number of Years After Menopause, Categorical 21 - ≤30 years	19 participants n=21 Participants	58 participants n=8 Participants	19 participants n=8 Participants	224 participants n=24 Participants	55 participants n=5 Participants	19 participants n=7 Participants	42 participants n=5 Participants	12 participants n=4 Participants
Number of Years After Menopause, Categorical ≥31 years	4 participants n=21 Participants	17 participants n=8 Participants	4 participants n=8 Participants	58 participants n=24 Participants	9 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants	7 participants n=4 Participants
Number of Years After Menopause, Categorical Unknown, But >2 years	9 participants n=21 Participants	36 participants n=8 Participants	12 participants n=8 Participants	161 participants n=24 Participants	38 participants n=5 Participants	12 participants n=7 Participants	44 participants n=5 Participants	10 participants n=4 Participants
Number of Years After Menopause	19.2 years STANDARD_DEVIATION 8.36 • n=21 Participants	19.5 years STANDARD_DEVIATION 8.41 • n=8 Participants	20.1 years STANDARD_DEVIATION 7.84 • n=8 Participants	18.7 years STANDARD_DEVIATION 8.28 • n=24 Participants	18.6 years STANDARD_DEVIATION 7.81 • n=5 Participants	20.2 years STANDARD_DEVIATION 8.72 • n=7 Participants	17.2 years STANDARD_DEVIATION 8.44 • n=5 Participants	18.3 years STANDARD_DEVIATION 8.28 • n=4 Participants
History of Bisphosphonate Administration Yes	9 participants n=21 Participants	26 participants n=8 Participants	6 participants n=8 Participants	98 participants n=24 Participants	19 participants n=5 Participants	6 participants n=7 Participants	24 participants n=5 Participants	8 participants n=4 Participants
History of Bisphosphonate Administration No	56 participants n=21 Participants	175 participants n=8 Participants	60 participants n=8 Participants	773 participants n=24 Participants	180 participants n=5 Participants	60 participants n=7 Participants	182 participants n=5 Participants	60 participants n=4 Participants
Timing of Initial Delayed Release (DR) Tablet Administration on Awakening Less than 30 Minutes before Breakfast	0 participants n=21 Participants	1 participants n=8 Participants	0 participants n=8 Participants	1 participants n=24 Participants	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Timing of Initial Delayed Release (DR) Tablet Administration on Awakening 0.5 to 1.5 Hours before Breakfast	53 participants n=21 Participants	164 participants n=8 Participants	50 participants n=8 Participants	707 participants n=24 Participants	165 participants n=5 Participants	56 participants n=7 Participants	167 participants n=5 Participants	52 participants n=4 Participants
Timing of Initial Delayed Release (DR) Tablet Administration on Awakening 1.5 to 2.5 Hours before Breakfast	8 participants n=21 Participants	27 participants n=8 Participants	15 participants n=8 Participants	135 participants n=24 Participants	29 participants n=5 Participants	8 participants n=7 Participants	35 participants n=5 Participants	13 participants n=4 Participants
Timing of Initial Delayed Release (DR) Tablet Administration on Awakening 2.5 to 4 Hours before Breakfast	4 participants n=21 Participants	8 participants n=8 Participants	1 participants n=8 Participants	27 participants n=24 Participants	5 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants	3 participants n=4 Participants
Lumbar Spine (L2-L4) Bone Mineral Density (BMD), Categorical Min - ≤0.707 g/cm^2	52 participants n=21 Participants	158 participants n=8 Participants	49 participants n=8 Participants	702 participants n=24 Participants	167 participants n=5 Participants	46 participants n=7 Participants	176 participants n=5 Participants	54 participants n=4 Participants
Lumbar Spine (L2-L4) Bone Mineral Density (BMD), Categorical 0.708 (70%YAM) - ≤0.808 g/cm^2	10 participants n=21 Participants	28 participants n=8 Participants	11 participants n=8 Participants	118 participants n=24 Participants	24 participants n=5 Participants	13 participants n=7 Participants	21 participants n=5 Participants	11 participants n=4 Participants
Lumbar Spine (L2-L4) Bone Mineral Density (BMD), Categorical 0.809 (80%YAM) g/cm^2 - ≤Max	3 participants n=21 Participants	14 participants n=8 Participants	6 participants n=8 Participants	50 participants n=24 Participants	8 participants n=5 Participants	7 participants n=7 Participants	9 participants n=5 Participants	3 participants n=4 Participants
L2-L4 (BMD)	0.6448 g/cm^2 STANDARD_DEVIATION 0.08909 • n=21 Participants	0.6589 g/cm^2 STANDARD_DEVIATION 0.09893 • n=8 Participants	0.6714 g/cm^2 STANDARD_DEVIATION 0.09999 • n=8 Participants	0.6564 g/cm^2 STANDARD_DEVIATION 0.09303 • n=24 Participants	0.6553 g/cm^2 STANDARD_DEVIATION 0.09060 • n=5 Participants	0.6690 g/cm^2 STANDARD_DEVIATION 0.11746 • n=7 Participants	0.6477 g/cm^2 STANDARD_DEVIATION 0.08037 • n=5 Participants	0.6633 g/cm^2 STANDARD_DEVIATION 0.08766 • n=4 Participants
L2-L4 BMD T-score, Categorical Min - ≤-2.500	53 participants n=21 Participants	160 participants n=8 Participants	51 participants n=8 Participants	711 participants n=24 Participants	169 participants n=5 Participants	47 participants n=7 Participants	177 participants n=5 Participants	54 participants n=4 Participants
L2-L4 BMD T-score, Categorical -2.499 - ≤-1.000	12 participants n=21 Participants	36 participants n=8 Participants	12 participants n=8 Participants	142 participants n=24 Participants	28 participants n=5 Participants	16 participants n=7 Participants	26 participants n=5 Participants	12 participants n=4 Participants
L2-L4 BMD T-score, Categorical -0.999 - ≤Max	0 participants n=21 Participants	4 participants n=8 Participants	3 participants n=8 Participants	17 participants n=24 Participants	2 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	2 participants n=4 Participants
L2-L4 BMD T-score	-3.0773 score on a scale STANDARD_DEVIATION 0.74863 • n=21 Participants	-2.9587 score on a scale STANDARD_DEVIATION 0.83135 • n=8 Participants	-2.8536 score on a scale STANDARD_DEVIATION 0.84030 • n=8 Participants	-2.9796 score on a scale STANDARD_DEVIATION 0.78178 • n=24 Participants	-2.9889 score on a scale STANDARD_DEVIATION 0.76130 • n=5 Participants	-2.8738 score on a scale STANDARD_DEVIATION 0.98709 • n=7 Participants	-3.0532 score on a scale STANDARD_DEVIATION 0.67537 • n=5 Participants	-2.9219 score on a scale STANDARD_DEVIATION 0.73670 • n=4 Participants
Total Proximal Femur BMD	0.6486 g/cm^2 STANDARD_DEVIATION 0.06973 • n=21 Participants	0.6652 g/cm^2 STANDARD_DEVIATION 0.08465 • n=8 Participants	0.6520 g/cm^2 STANDARD_DEVIATION 0.07289 • n=8 Participants	0.6548 g/cm^2 STANDARD_DEVIATION 0.08464 • n=24 Participants	0.6553 g/cm^2 STANDARD_DEVIATION 0.08997 • n=5 Participants	0.6573 g/cm^2 STANDARD_DEVIATION 0.09537 • n=7 Participants	0.6452 g/cm^2 STANDARD_DEVIATION 0.08490 • n=5 Participants	0.6580 g/cm^2 STANDARD_DEVIATION 0.07982 • n=4 Participants
Total Proximal Femur BMD T-score	-2.2642 score on a scale STANDARD_DEVIATION 0.69731 • n=21 Participants	-2.0978 score on a scale STANDARD_DEVIATION 0.84652 • n=8 Participants	-2.2305 score on a scale STANDARD_DEVIATION 0.72892 • n=8 Participants	-2.2021 score on a scale STANDARD_DEVIATION 0.84645 • n=24 Participants	-2.1972 score on a scale STANDARD_DEVIATION 0.89971 • n=5 Participants	-2.1770 score on a scale STANDARD_DEVIATION 0.95369 • n=7 Participants	-2.2982 score on a scale STANDARD_DEVIATION 0.84903 • n=5 Participants	-2.1699 score on a scale STANDARD_DEVIATION 0.79822 • n=4 Participants
Trochanter BMD	0.4879 g/cm^2 STANDARD_DEVIATION 0.05653 • n=21 Participants	0.5009 g/cm^2 STANDARD_DEVIATION 0.06626 • n=8 Participants	0.4900 g/cm^2 STANDARD_DEVIATION 0.06824 • n=8 Participants	0.4925 g/cm^2 STANDARD_DEVIATION 0.06914 • n=24 Participants	0.4938 g/cm^2 STANDARD_DEVIATION 0.07793 • n=5 Participants	0.4954 g/cm^2 STANDARD_DEVIATION 0.06803 • n=7 Participants	0.4844 g/cm^2 STANDARD_DEVIATION 0.06610 • n=5 Participants	0.4932 g/cm^2 STANDARD_DEVIATION 0.07164 • n=4 Participants
Femoral Neck BMD	0.5245 g/cm^2 STANDARD_DEVIATION 0.06293 • n=21 Participants	0.5411 g/cm^2 STANDARD_DEVIATION 0.08051 • n=8 Participants	0.5373 g/cm^2 STANDARD_DEVIATION 0.07346 • n=8 Participants	0.5327 g/cm^2 STANDARD_DEVIATION 0.07712 • n=24 Participants	0.5318 g/cm^2 STANDARD_DEVIATION 0.07695 • n=5 Participants	0.5258 g/cm^2 STANDARD_DEVIATION 0.08147 • n=7 Participants	0.5278 g/cm^2 STANDARD_DEVIATION 0.07960 • n=5 Participants	0.5348 g/cm^2 STANDARD_DEVIATION 0.07154 • n=4 Participants
Femoral Neck BMD T-score	-2.9501 score on a scale STANDARD_DEVIATION 0.69920 • n=21 Participants	-2.7652 score on a scale STANDARD_DEVIATION 0.89454 • n=8 Participants	-2.8077 score on a scale STANDARD_DEVIATION 0.81618 • n=8 Participants	-2.8594 score on a scale STANDARD_DEVIATION 0.85690 • n=24 Participants	-2.8683 score on a scale STANDARD_DEVIATION 0.85505 • n=5 Participants	-2.9358 score on a scale STANDARD_DEVIATION 0.90523 • n=7 Participants	-2.9135 score on a scale STANDARD_DEVIATION 0.88448 • n=5 Participants	-2.8360 score on a scale STANDARD_DEVIATION 0.79487 • n=4 Participants
Dual-Energy X-Ray Absorptiometry (DXA) Measuring Apparatus QDR-4500	6 participants n=21 Participants	12 participants n=8 Participants	6 participants n=8 Participants	62 participants n=24 Participants	14 participants n=5 Participants	5 participants n=7 Participants	14 participants n=5 Participants	5 participants n=4 Participants
Dual-Energy X-Ray Absorptiometry (DXA) Measuring Apparatus Delphi	9 participants n=21 Participants	26 participants n=8 Participants	8 participants n=8 Participants	118 participants n=24 Participants	28 participants n=5 Participants	9 participants n=7 Participants	29 participants n=5 Participants	9 participants n=4 Participants
Dual-Energy X-Ray Absorptiometry (DXA) Measuring Apparatus Discovery	35 participants n=21 Participants	118 participants n=8 Participants	35 participants n=8 Participants	499 participants n=24 Participants	114 participants n=5 Participants	38 participants n=7 Participants	120 participants n=5 Participants	39 participants n=4 Participants
Dual-Energy X-Ray Absorptiometry (DXA) Measuring Apparatus Explorer	15 participants n=21 Participants	45 participants n=8 Participants	17 participants n=8 Participants	192 participants n=24 Participants	43 participants n=5 Participants	14 participants n=7 Participants	43 participants n=5 Participants	15 participants n=4 Participants
Number of Existing Vertebral (Thoracic [Th4] -L4) Fractures 0	38 participants n=21 Participants	121 participants n=8 Participants	35 participants n=8 Participants	531 participants n=24 Participants	138 participants n=5 Participants	32 participants n=7 Participants	125 participants n=5 Participants	42 participants n=4 Participants
Number of Existing Vertebral (Thoracic [Th4] -L4) Fractures 1	18 participants n=21 Participants	58 participants n=8 Participants	25 participants n=8 Participants	239 participants n=24 Participants	39 participants n=5 Participants	21 participants n=7 Participants	61 participants n=5 Participants	17 participants n=4 Participants
Number of Existing Vertebral (Thoracic [Th4] -L4) Fractures 2	6 participants n=21 Participants	15 participants n=8 Participants	6 participants n=8 Participants	66 participants n=24 Participants	12 participants n=5 Participants	8 participants n=7 Participants	12 participants n=5 Participants	7 participants n=4 Participants
Number of Existing Vertebral (Thoracic [Th4] -L4) Fractures ≥3	3 participants n=21 Participants	6 participants n=8 Participants	0 participants n=8 Participants	34 participants n=24 Participants	10 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants	2 participants n=4 Participants
Fragility Fracture Yes	31 participants n=21 Participants	104 participants n=8 Participants	36 participants n=8 Participants	417 participants n=24 Participants	86 participants n=5 Participants	37 participants n=7 Participants	91 participants n=5 Participants	32 participants n=4 Participants
Fragility Fracture No	34 participants n=21 Participants	97 participants n=8 Participants	30 participants n=8 Participants	454 participants n=24 Participants	113 participants n=5 Participants	29 participants n=7 Participants	115 participants n=5 Participants	36 participants n=4 Participants
Primary Osteoporosis Diagnosis Criteria 2012 Fragility Fracture (Vertebrae or Proximal Femur)	25 participants n=21 Participants	80 participants n=8 Participants	32 participants n=8 Participants	343 participants n=24 Participants	65 participants n=5 Participants	30 participants n=7 Participants	82 participants n=5 Participants	29 participants n=4 Participants
Primary Osteoporosis Diagnosis Criteria 2012 Fragility Fracture (Other and BMD<YAM*80%)	6 participants n=21 Participants	24 participants n=8 Participants	4 participants n=8 Participants	74 participants n=24 Participants	21 participants n=5 Participants	7 participants n=7 Participants	9 participants n=5 Participants	3 participants n=4 Participants
Primary Osteoporosis Diagnosis Criteria 2012 No Fragility Fracture and BMD<=YAM*70%	34 participants n=21 Participants	97 participants n=8 Participants	30 participants n=8 Participants	453 participants n=24 Participants	113 participants n=5 Participants	29 participants n=7 Participants	115 participants n=5 Participants	35 participants n=4 Participants
Serum 25-hydroxy Vitamin D (25-OH-D), Categorical Min - ≤14.9 ng/mL	8 participants n=21 Participants	21 participants n=8 Participants	8 participants n=8 Participants	89 participants n=24 Participants	18 participants n=5 Participants	8 participants n=7 Participants	21 participants n=5 Participants	5 participants n=4 Participants
Serum 25-hydroxy Vitamin D (25-OH-D), Categorical 15.0 - ≤27.9 ng/mL	50 participants n=21 Participants	160 participants n=8 Participants	53 participants n=8 Participants	685 participants n=24 Participants	161 participants n=5 Participants	51 participants n=7 Participants	157 participants n=5 Participants	53 participants n=4 Participants
Serum 25-hydroxy Vitamin D (25-OH-D), Categorical 28.0 ng/mL - ≤Max	7 participants n=21 Participants	19 participants n=8 Participants	5 participants n=8 Participants	96 participants n=24 Participants	20 participants n=5 Participants	7 participants n=7 Participants	28 participants n=5 Participants	10 participants n=4 Participants
Serum 25-OH-D	21.17 ng/mL STANDARD_DEVIATION 5.248 • n=21 Participants	21.52 ng/mL STANDARD_DEVIATION 5.121 • n=8 Participants	20.58 ng/mL STANDARD_DEVIATION 4.761 • n=8 Participants	21.42 ng/mL STANDARD_DEVIATION 5.288 • n=24 Participants	21.55 ng/mL STANDARD_DEVIATION 5.266 • n=5 Participants	21.44 ng/mL STANDARD_DEVIATION 5.423 • n=7 Participants	21.46 ng/mL STANDARD_DEVIATION 5.592 • n=5 Participants	21.64 ng/mL STANDARD_DEVIATION 5.427 • n=4 Participants
Serum C-telopeptide of Type 1 Collagen (CTX)	0.497 ng/mL STANDARD_DEVIATION 0.1867 • n=21 Participants	0.417 ng/mL STANDARD_DEVIATION 0.1592 • n=8 Participants	0.399 ng/mL STANDARD_DEVIATION 0.1613 • n=8 Participants	0.434 ng/mL STANDARD_DEVIATION 0.1696 • n=24 Participants	0.444 ng/mL STANDARD_DEVIATION 0.1660 • n=5 Participants	0.460 ng/mL STANDARD_DEVIATION 0.1855 • n=7 Participants	0.426 ng/mL STANDARD_DEVIATION 0.1776 • n=5 Participants	0.421 ng/mL STANDARD_DEVIATION 0.1437 • n=4 Participants
Serum Bone-type Alkaline Phosphatase (BAP)	17.17 μg/L STANDARD_DEVIATION 7.354 • n=21 Participants	15.13 μg/L STANDARD_DEVIATION 5.164 • n=8 Participants	15.13 μg/L STANDARD_DEVIATION 6.815 • n=8 Participants	15.79 μg/L STANDARD_DEVIATION 6.142 • n=24 Participants	15.91 μg/L STANDARD_DEVIATION 5.809 • n=5 Participants	16.88 μg/L STANDARD_DEVIATION 8.617 • n=7 Participants	15.83 μg/L STANDARD_DEVIATION 6.035 • n=5 Participants	15.45 μg/L STANDARD_DEVIATION 5.024 • n=4 Participants
Serum Tartrate-resistant Acid Phosphatase 5b (TRACP-5b)	444.7 mU/dL STANDARD_DEVIATION 142.90 • n=21 Participants	410.5 mU/dL STANDARD_DEVIATION 142.09 • n=8 Participants	395.0 mU/dL STANDARD_DEVIATION 128.38 • n=8 Participants	418.5 mU/dL STANDARD_DEVIATION 148.29 • n=24 Participants	427.1 mU/dL STANDARD_DEVIATION 154.67 • n=5 Participants	424.1 mU/dL STANDARD_DEVIATION 144.89 • n=7 Participants	422.1 mU/dL STANDARD_DEVIATION 162.07 • n=5 Participants	398.4 mU/dL STANDARD_DEVIATION 127.54 • n=4 Participants
Serum Procollagen 1 N-terminal Peptide (P1NP)	53.43 μg/L STANDARD_DEVIATION 22.783 • n=21 Participants	48.53 μg/L STANDARD_DEVIATION 20.366 • n=8 Participants	46.04 μg/L STANDARD_DEVIATION 21.714 • n=8 Participants	50.44 μg/L STANDARD_DEVIATION 21.648 • n=24 Participants	51.79 μg/L STANDARD_DEVIATION 20.357 • n=5 Participants	54.91 μg/L STANDARD_DEVIATION 27.552 • n=7 Participants	50.89 μg/L STANDARD_DEVIATION 22.635 • n=5 Participants	47.83 μg/L STANDARD_DEVIATION 17.120 • n=4 Participants
Urine Type 1 Collagen Cross-linked N-telopeptide (NTX)	64.44 nmol BCE/mmol-CRE STANDARD_DEVIATION 29.535 • n=21 Participants	54.48 nmol BCE/mmol-CRE STANDARD_DEVIATION 23.988 • n=8 Participants	53.66 nmol BCE/mmol-CRE STANDARD_DEVIATION 23.911 • n=8 Participants	56.24 nmol BCE/mmol-CRE STANDARD_DEVIATION 25.871 • n=24 Participants	56.76 nmol BCE/mmol-CRE STANDARD_DEVIATION 26.169 • n=5 Participants	61.04 nmol BCE/mmol-CRE STANDARD_DEVIATION 34.808 • n=7 Participants	54.98 nmol BCE/mmol-CRE STANDARD_DEVIATION 23.928 • n=5 Participants	53.77 nmol BCE/mmol-CRE STANDARD_DEVIATION 22.739 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline and End of Study (up to Month 12)

Population: Full Analysis Set (FAS), all randomized participants who received at least 1 dose of study drug, with data available for analyses.

The change in BMD in the second to the fourth lumbar vertebrae, L2 to L4, and the averages of L2 to L4 at end of study relative to baseline. DXA is a means of measuring BMD through x-ray.

Outcome measures

Outcome measures
Measure	NE-58095 IR 2.5 mg Once Daily on Awakening n=190 Participants NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly Following Breakfast n=194 Participants NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly Following Breakfast n=181 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Percent Change From Baseline in Mean Lumbar Spine (L2-L4) Bone Mineral Density (BMD) Measured by Dual Energy X-Ray Absorptiometry (DXA) at End of Study	5.07 percent change Standard Deviation 4.749	3.36 percent change Standard Deviation 4.332	4.11 percent change Standard Deviation 4.654	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12)

Population: FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses. "n" in the category is the number of participants with data available at the given time-point.

The change in BMD in each vertebra, L2 to L4, and the averages of L2 to L4 at each visit relative to baseline. DXA is a means of measuring BMD through x-ray.

Outcome measures

Outcome measures
Measure	NE-58095 IR 2.5 mg Once Daily on Awakening n=199 Participants NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly Following Breakfast n=66 Participants NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly Following Breakfast n=206 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast n=68 Participants NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly on Awakening n=65 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly Following Breakfast n=200 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast n=66 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Percent Change From Baseline in Mean Lumbar Spine (L2-L4) BMD Measured by DXA at Each Visit Month 6 (n=190, 62, 194, 61, 59, 181, 63)	3.18 percent change Standard Deviation 4.211	1.73 percent change Standard Deviation 3.635	1.92 percent change Standard Deviation 4.124	2.40 percent change Standard Deviation 3.408	3.67 percent change Standard Deviation 4.841	2.70 percent change Standard Deviation 4.117	2.64 percent change Standard Deviation 4.907
Percent Change From Baseline in Mean Lumbar Spine (L2-L4) BMD Measured by DXA at Each Visit Month 12 (n=178, 58, 180, 58, 55, 171, 60)	5.00 percent change Standard Deviation 4.783	3.83 percent change Standard Deviation 4.227	3.53 percent change Standard Deviation 4.423	3.98 percent change Standard Deviation 3.784	5.04 percent change Standard Deviation 4.387	4.05 percent change Standard Deviation 4.518	4.38 percent change Standard Deviation 5.277
Percent Change From Baseline in Mean Lumbar Spine (L2-L4) BMD Measured by DXA at Each Visit End of Study (n=190, 62, 194, 61, 59, 181, 63)	5.07 percent change Standard Deviation 4.749	3.82 percent change Standard Deviation 4.158	3.36 percent change Standard Deviation 4.332	3.93 percent change Standard Deviation 3.714	4.81 percent change Standard Deviation 4.383	4.11 percent change Standard Deviation 4.654	4.36 percent change Standard Deviation 5.150

SECONDARY outcome

Timeframe: Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12)

The change in BMD in the total proximal femur (whole bone, trochanteric region, and neck region) at each visit relative to baseline. DXA is a means of measuring BMD through x-ray.

Outcome measures

Outcome measures
Measure	NE-58095 IR 2.5 mg Once Daily on Awakening n=199 Participants NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly Following Breakfast n=66 Participants NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly Following Breakfast n=206 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast n=68 Participants NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly on Awakening n=65 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly Following Breakfast n=200 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast n=66 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Percent Change From Baseline in Femur (Total Proximal Femur) BMD Measured by DXA at Each Visit Month 6 (n=189, 62, 194, 61, 59, 180, 63)	1.10 percent change Standard Deviation 2.782	0.91 percent change Standard Deviation 2.665	0.43 percent change Standard Deviation 2.666	0.54 percent change Standard Deviation 2.404	0.77 percent change Standard Deviation 2.401	0.78 percent change Standard Deviation 2.420	0.55 percent change Standard Deviation 2.390
Percent Change From Baseline in Femur (Total Proximal Femur) BMD Measured by DXA at Each Visit Month 12 (n=181, 58, 180, 59, 55, 172, 61)	2.01 percent change Standard Deviation 3.316	1.32 percent change Standard Deviation 3.399	0.95 percent change Standard Deviation 3.233	1.15 percent change Standard Deviation 3.182	1.38 percent change Standard Deviation 3.013	1.45 percent change Standard Deviation 2.580	1.48 percent change Standard Deviation 2.880
Percent Change From Baseline in Femur (Total Proximal Femur) BMD Measured by DXA at Each Visit End of Study (n=189, 62, 194, 61, 59, 180, 63)	1.96 percent change Standard Deviation 3.288	1.30 percent change Standard Deviation 3.309	0.89 percent change Standard Deviation 3.172	1.15 percent change Standard Deviation 3.131	1.33 percent change Standard Deviation 2.948	1.45 percent change Standard Deviation 2.565	1.39 percent change Standard Deviation 2.873

SECONDARY outcome

Timeframe: Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12)

The change in BMD in the femur (trochanter) at each visit relative to baseline. DXA is a means of measuring BMD through x-ray.

Outcome measures

Outcome measures
Measure	NE-58095 IR 2.5 mg Once Daily on Awakening n=199 Participants NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly Following Breakfast n=66 Participants NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly Following Breakfast n=206 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast n=68 Participants NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly on Awakening n=65 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly Following Breakfast n=200 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.	NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast n=66 Participants NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Percent Change From Baseline in Femur (Trochanter) BMD Measured by DXA at Each Visit Month 6 (n=189, 62, 194, 61, 59, 180, 63)	1.34 percent change Standard Deviation 4.854	1.57 percent change Standard Deviation 3.832	0.70 percent change Standard Deviation 4.324	0.80 percent change Standard Deviation 3.500	1.46 percent change Standard Deviation 3.495	1.09 percent change Standard Deviation 3.141	0.53 percent change Standard Deviation 4.432
Percent Change From Baseline in Femur (Trochanter) BMD Measured by DXA at Each Visit End of Study (n=189, 62, 194, 61, 59, 180, 63)	2.52 percent change Standard Deviation 5.938	1.67 percent change Standard Deviation 3.951	1.35 percent change Standard Deviation 4.551	1.64 percent change Standard Deviation 4.038	2.42 percent change Standard Deviation 4.005	1.94 percent change Standard Deviation 3.661	1.85 percent change Standard Deviation 4.203
Percent Change From Baseline in Femur (Trochanter) BMD Measured by DXA at Each Visit Month 12 (n=181, 58, 180, 59, 55, 172, 61)	2.59 percent change Standard Deviation 6.007	1.80 percent change Standard Deviation 4.030	1.36 percent change Standard Deviation 4.632	1.66 percent change Standard Deviation 4.095	2.47 percent change Standard Deviation 4.129	1.94 percent change Standard Deviation 3.722	1.90 percent change Standard Deviation 4.259

SECONDARY outcome

Timeframe: Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12)

The change in BMD in the femur (femoral neck) at each visit relative to baseline. DXA is a means of measuring BMD through x-ray.