A Study for the Transdermal Application of Teriparatide

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01011556
• Collaborator: TransPharma Medical (Industry)
• Enrollment: 233
• Locations: 18
• Arms: 4
• Duration (Months): 22
• Patients Per Site: 12.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The primary purpose of this study is to help answer the following research questions:

1. How teriparatide given using a skin patch (transferred through the skin using the ViaDerm Teriparatide System) compares to teriparatide injected under the skin with a needle (pen injector) affects your bone density (how solid or porous your bones are).

2. The safety of the teriparatide skin patch and any side effects that might be associated with it.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis	Drug: Subcutaneous Teriparatide; Drug: Transdermal Teriparatide	Phase 2

Detailed Description

Teriparatide 20 micrograms (mcg) per day is currently only available as a subcutaneous (SQ) injection and many patients with severe osteoporosis for whom anabolic therapy with teriparatide is appropriate are either unwilling or physically unable to self-inject. The purpose of this Phase 2 study is to identify a transdermal dose or doses that will be comparable to the teriparatide 20 mcg SQ dose from a pharmacodynamic (PD) and safety standpoint for use in future Phase 3 studies.

Study Design

• Study Type: Interventional
• Actual Enrollment: 233 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study for Transdermal Application of Teriparatide
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 20 mcg Subcutaneous Teriparatide Received 20 micrograms (mcg) subcutaneously once daily in an unblinded manner.	Drug: Subcutaneous Teriparatide; Administered subcutaneously once daily for 12 months; Other Names: recombinant human parathyroid hormone (rhPTH) (1-34) recombinant human teriparatide Forteo Forsteo LY333334
Experimental: 30 mcg Transdermal Teriparatide Received 30 micrograms (mcg) teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Drug: Transdermal Teriparatide; Administered transdermally, applied once daily for 6 hours over 12 months; Other Names: synthetic human parathyroid hormone (shPTH) (1-34) synthetic human teriparatide
Experimental: 50 mcg Transdermal Teriparatide Received 50 micrograms (mcg) teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Drug: Transdermal Teriparatide; Administered transdermally, applied once daily for 6 hours over 12 months; Other Names: synthetic human parathyroid hormone (shPTH) (1-34) synthetic human teriparatide
Experimental: 80 mcg Transdermal Teriparatide Received 80 micrograms (mcg) teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Drug: Transdermal Teriparatide; Administered transdermally, applied once daily for 6 hours over 12 months; Other Names: synthetic human parathyroid hormone (shPTH) (1-34) synthetic human teriparatide

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months [Baseline, 12 Months]

   Bone mineral density (BMD) of the lumbar spine was assessed by dual energy X-ray absorptiometry (DXA). BMD values are corrected data and have been standardized across the machine types (Hologic and Lunar). Analyses were performed using ANCOVA model and least square (LS) means were adjusted for baseline BMD values as a covariate and pooled site and treatment as fixed effects.

Secondary Outcome Measures

1. Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 6 Months [Baseline, 6 Months]

   Bone mineral density (BMD) of the lumbar spine was assessed by dual energy X-ray absorptiometry (DXA). BMD values are corrected data and have been standardized across the machine types (Hologic and Lunar). Analyses were performed using ANCOVA model with the baseline value as a covariate and pooled site and treatment as fixed effects.

2. Time Course Change of BMD Response at the Lumbar Spine [Baseline to 6 Months and 12 Months]

   To assess the time course of the treatment, the BMD data of the lumbar spine was assessed by dual energy X-ray absorptiometry (DXA) and analyzed using a mixed model repeated measures (MMRM) method, with the repeated measure occurring at each visit (for example, 6 and 12 month). BMD values are corrected data and have been standardized across the machine types (Hologic and Lunar).

3. Percent Change From Baseline in Procollagen Type 1 N-Terminal Propeptide (P1NP) [Baseline, 1 Month, 3 Months, 6 Months, 12 Months]

   Procollagen Type 1 N-Terminal Propeptide (P1NP) is a marker of bone formation.

4. Percent Change From Baseline of C-Terminal Telopeptide (CTX) [Baseline, 1 Month, 3 Months, 6 Months, 12 Months]

   C-terminal telopeptide is a marker of bone resorption.

5. Percent Change From Baseline in Serum Procollagen Type 1 C-Propeptide (P1CP) at 1 Month [Baseline, 1 Month]

   Procollagen Type 1 N-Terminal Propeptide (P1NP) is a marker of bone formation.

6. Convenience/Ease of Use Questionnaire (CEUQ) [baseline up to 12 months]

   CEUQ consists of 5 sections and 16 questions using a 5-point Likert scale designed to collect measures for ease of use (S1), convenience of use (S2), confidence of use (S3), fear of use (S4), and overall satisfaction with therapy (S5). CEUQ is not a validated instrument.

7. Change in Serum Calcium With and Without Adjustments for Serum Albumin From Predose to After 4 and 6 Hours [Baseline, 12 Months]

   Serum calcium adjusted for serum albumin levels is calculated using the following formula: Total Calcium + [(40 - albumin) x 0.02]. Analysis for serum calcium and albumin adjusted serum calcium were collected at predose, 4 hours (h) post-dose (PD) and 6 h PD at baseline and 12 months (mon).

8. Change From Baseline in Urine Calcium Excretion at 6 and 12 Months [Baseline, 6 Months, 12 Months]

9. Change From Pre-dose and Postdose Supine and Standing SBP and DBP at Baseline (BL) and 12 Months (Mon) [Pre-Dose, 30 minutes, 2 hours Post-Dose at Baseline and 12 Months]

   Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) measured at pre-dose and 30 minutes (min) and 2 hours (hr) post-dose in both the supine and standing position.

10. Change From Pre-dose to Postdose in Supine and Standing Heart Rate at Baseline (BL) and 12 Months (Mon). [Pre-dose, 30 minutes, 2 hours at Baseline and 12 Months]

11. Number of Participants With Parathyroid Hormone (PTH) Specific Antibody Levels [Baseline and 1, 3, 12, and 13 Months (mon)]

    Participants were tested for anti-recombinant teriparatide and anti-synthetic teriparatide titers. Either none were detected (ND) or antibodies were determined to be present if the teriparatide specific antibody titers were at least 1:8 (titer 1:8).

12. Pharmacokinetics Parameters: Area Under the Curve (AUC) [Baseline, 1 Month, 3 Months, and 12 Months]

    Due to high intra-subject variability, data was not analyzed for this outcome measure.

13. Pharmacokinetics Parameters: Maximal Concentration (Cmax) [Baseline, 1 Month, 3 Months, 12 Months]

    Due to high intra-subject variability, data was not analyzed for this outcome measure.

14. DRAIZE Edema Assessment at Baseline Through 13 Month Follow-up [13 Month follow-up]

    Severity of edema was categorized based on a 5 point scale: 0=no edema, 4=severe edema (defined as an area raised more than 1 millimeter and extending beyond area of exposure)

15. DRAIZE Erythema Assessment at Baseline Through 13 Month Follow-up [13 Month follow-up]

    Severity of erythema was categorized based on a 5 point scale: 0=no erythema, 4=severe erythema (defined as beet red to eschar)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 80 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ambulatory, postmenopausal women.

• Centrally confirmed lumbar spine or femoral neck bone mineral density (BMD) T-score of less than or equal to -2.5.

• Without language barrier, cooperative, expected to return for all follow-up procedures, and have given informed consent after being informed of the risks, medications, and procedures to be used in the study.

• Able to use the pen-type injection delivery system and the ViaDerm Teriparatide System satisfactorily in the opinion of the investigator, or with the help of a family member or caregiver.

• Able to be reached by telephone for follow-up contact between visits

Exclusion Criteria:

• Abnormal laboratory values for albumin and alkaline phosphatase.

• Laboratory values outside the ranges defined in the protocol for the following: Serum calcium, intact parathyroid hormone (iPTH), 25 hydroxyvitamin D, and 24-hour urine calcium

• History of diseases other than postmenopausal osteoporosis that affect bone metabolism, such as Paget's disease, renal osteodystrophy, osteomalacia, any secondary causes of osteoporosis, hypoparathyroidism, hyperparathyroidism, and intestinal malabsorption.

• History of malignant neoplasms in the 5 years prior to randomization, with the exception of superficial basal cell carcinoma or squamous cell carcinoma of the skin that has been definitively treated. Patients with carcinoma in situ of the uterine cervix treated definitively more than 1 year prior to entry into the study may be randomized.

• Use of a pacemaker.

• Known chronic dermatological disorder, such as contact dermatitis

• History of allergy or sensitivity to tapes or adhesives

• Patients prone to bleeding with coagulopathies, such as hemophilia or thrombocytopenia.

• Patients who have an increased baseline risk of osteosarcoma, Paget's disease of the bone, or unexplained elevations of alkaline phosphatase; or prior external beam, implant radiation therapy involving the skeleton, or previous primary skeletal malignancy.

• Major fracture within the past year in the femur, tibia, humerus, or radius (with or without ulna).

Treatment with:

• calcitonins in the 2 months prior to randomization.

• oral, transdermal/patch, or injectable estrogens, progestins, estrogen analogs, estrogen agonists, estrogen antagonists, selective estrogen receptor modulators, or tibolone in the 3 months prior to randomization; treatment with intravaginal estrogens in doses higher than 0.3 mg of conjugated equine estrogen, or the equivalent, for more than 3 doses per week in the 3 months prior to randomization.

• androgens or other anabolic steroids in the 6 months prior to randomization.

• fluorides in the 2 years prior to randomization. (Previous or current use of fluoridated water or topical dental fluoride treatments are permitted.)

• oral bisphosphonates for more than 2 consecutive months in the 6 months prior to randomization; treatment with intravenous bisphosphonates in the 6 months prior to randomization; treatment with more than 1 cycle of intermittent oral bisphosphonates in the 6 months prior to randomization; or having received the last cycle of this intermittent oral regimen less than 4 weeks prior to screening.

• patients receiving intravenous zoledronic acid during the 12 months prior to randomization.

• vitamin D greater than 50,000 International Units (IU) per week or with any dose of calcitriol or vitamin D analogs or agonists in the 6 months prior to randomization.

• systemic corticosteroids in the 1 month prior to randomization or for more than 30 days in the 1 year prior to randomization. (Ophthalmic, otic, topical, orally inhaled, nasally inhaled, or intra-articular corticosteroid therapy may be used without these restrictions.)

• any other drug known to significantly affect bone metabolism in the 6 months prior to randomization.

• warfarin or other coumadin anticoagulants in the 1 month prior to randomization.

• any investigational drug in the 1 month prior to entry into the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Buenos Aires		Argentina	C1128AAF
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Parnu		Estonia	80010
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tallin		Estonia	10138
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tartu		Estonia	50410
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Balatonfured		Hungary	8230
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Budapest		Hungary	1036
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Debrecen		Hungary	4043
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Esztergom		Hungary	2500
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gyor		Hungary	9023
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Szombathely		Hungary	H-9700
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tatabanya		Hungary	2800
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Guadalajara		Mexico	44158
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mexico City		Mexico	03300
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Monterrey		Mexico	64460
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bucharest		Romania	011025
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cluj-Napoca		Romania	400006
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lasi		Romania	700111
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Timisoara		Romania	300736

Sponsors and Collaborators

• Eli Lilly and Company
• TransPharma Medical

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01011556
• Other Study ID Numbers: 12641; I2Y-MC-GHFA(c)
• First Posted: Nov 11, 2009
• Last Update Posted: Oct 23, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by Eli Lilly and Company: Age Related Osteoporosis; Senile Osteoporosis
• Additional relevant MeSH terms: Osteoporosis; Teriparatide; Hormones; Parathyroid Hormone

Study Results

Participant Flow

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Period Title: Overall Study
STARTED	58	56	55	64
Received at Least 1 Dose of Study Drug	57	56	54	64
COMPLETED	52	48	45	51
NOT COMPLETED	6	8	10	13

Baseline Characteristics

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide	Total
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Total of all reporting groups
Overall Participants	57	56	54	64	231
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.9 (7.2)	65.0 (8.3)	67.6 (8.4)	65.1 (7.2)	65.4 (7.8)
Sex: Female, Male (Count of Participants)
Female	57 100%	56 100%	54 100%	64 100%	231 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	14 24.6%	15 26.8%	14 25.9%	17 26.6%	60 26%
Latin American	0 0%	2 3.6%	1 1.9%	0 0%	3 1.3%
Mexican	7 12.3%	6 10.7%	5 9.3%	6 9.4%	24 10.4%
Not Hispanic or Latino	33 57.9%	32 57.1%	32 59.3%	40 62.5%	137 59.3%
South American	1 1.8%	1 1.8%	1 1.9%	0 0%	3 1.3%
Spaniard	2 3.5%	0 0%	1 1.9%	1 1.6%	4 1.7%
Region of Enrollment (participants) [Number]
Estonia	4 7%	1 1.8%	6 11.1%	4 6.3%	15 6.5%
Hungary	21 36.8%	25 44.6%	23 42.6%	25 39.1%	94 40.7%
Mexico	7 12.3%	6 10.7%	5 9.3%	6 9.4%	24 10.4%
Argentina	17 29.8%	17 30.4%	16 29.6%	18 28.1%	68 29.4%
Romania	8 14%	7 12.5%	4 7.4%	11 17.2%	30 13%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months
Description	Bone mineral density (BMD) of the lumbar spine was assessed by dual energy X-ray absorptiometry (DXA). BMD values are corrected data and have been standardized across the machine types (Hologic and Lunar). Analyses were performed using ANCOVA model and least square (LS) means were adjusted for baseline BMD values as a covariate and pooled site and treatment as fixed effects.
Time Frame	Baseline, 12 Months

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of drug and had at least 1 baseline and post-baseline lumbar spine BMD measure. Analysis was performed using intention-to-treat (ITT) principle, last observation carried forward method and ANCOVA model.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 micrograms (mcg) teriparatide subcutaneously once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	54	54	51	60
Least Squares Mean (90% Confidence Interval) [percentage change in BMD]	7.80	0.63	0.32	1.63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 30 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A noninferiority margin of 3.5% was used.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Analyses were performed using ANCOVA model with the baseline value as a covariate and pooled site and treatment as fixed effects.
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-7.17
	Confidence Interval	(2-Sided) 90%; -8.489 to -5.851
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 50 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A noninferiority margin of 3.5% was used.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Analyses were performed using ANCOVA model with the baseline value as a covariate and pooled site and treatment as fixed effects.
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-7.48
	Confidence Interval	(2-Sided) 90%; -8.822 to -6.144
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 80 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A noninferiority margin of 3.5% was used.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Analyses were performed using ANCOVA model with the baseline value as a covariate and pooled site and treatment as fixed effects.
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-6.17
	Confidence Interval	(2-Sided) 90%; -7.448 to -4.891
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 6 Months
Description	Bone mineral density (BMD) of the lumbar spine was assessed by dual energy X-ray absorptiometry (DXA). BMD values are corrected data and have been standardized across the machine types (Hologic and Lunar). Analyses were performed using ANCOVA model with the baseline value as a covariate and pooled site and treatment as fixed effects.
Time Frame	Baseline, 6 Months

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of drug and had at least 1 baseline and post-baseline lumbar spine BMD measure. Analysis was performed using intent-to-treat principal, last observation carried forward method and ANCOVA model.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	54	52	51	58
Least Squares Mean (90% Confidence Interval) [percentage change in BMD]	4.74	0.16	0.88	1.19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 30 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Analyses were performed using ANCOVA model with the baseline value as a covariate and pooled site and treatment as fixed effects.
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-4.58
	Confidence Interval	(2-Sided) 90%; -5.716 to -3.452
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 50 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Analyses were performed using ANCOVA model with the baseline value as a covariate and pooled site and treatment as fixed effects.
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-3.87
	Confidence Interval	(2-Sided) 90%; -5.006 to -2.727
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 80 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Analyses were performed using ANCOVA model with the baseline value as a covariate and pooled site and treatment as fixed effects.
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-3.56
	Confidence Interval	(2-Sided) 90%; -4.652 to -2.464
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Time Course Change of BMD Response at the Lumbar Spine
Description	To assess the time course of the treatment, the BMD data of the lumbar spine was assessed by dual energy X-ray absorptiometry (DXA) and analyzed using a mixed model repeated measures (MMRM) method, with the repeated measure occurring at each visit (for example, 6 and 12 month). BMD values are corrected data and have been standardized across the machine types (Hologic and Lunar).
Time Frame	Baseline to 6 Months and 12 Months

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of drug, had at least 1 baseline and post-baseline lumbar spine BMD measure. Analysis was performed using ITT principal.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	57	56	54	63
6 months (n=54, 52, 51, 58)	4.72	0.19	0.78	1.19
12 months (n=52, 48, 45, 50)	8.12	0.62	0.66	1.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 30 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-value is for change in BMD at 6 months
	Method	Mixed Models Analysis
	Comments	MMRM Model: Percentage change in BMD = treatment+baseline+pooled site+visit+treatment*visit interaction. Repeat measure occurred at each visit.
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-4.53
	Confidence Interval	(2-Sided) 90%; -5.663 to -3.392
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.687
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 50 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-value is for change in BMD at 6 months
	Method	Mixed Models Analysis
	Comments	MMRM Model: Percentage change in BMD = treatment+baseline+pooled site+visit+treatment*visit interaction. Repeat measure occurred at each visit.
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-3.94
	Confidence Interval	(2-Sided) 90%; -5.086 to -2.800
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.692
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 80 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-value is for change in BMD at 6 months
	Method	Mixed Models Analysis
	Comments	MMRM Model: Percentage change in BMD = treatment+baseline+pooled site+visit+treatment*visit interaction. Repeat measure occurred at each visit.
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-3.53
	Confidence Interval	(2-Sided) 90%; -4.627 to -2.430
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.665
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 30 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-value is for change in BMD at 12 months
	Method	Mixed Models Analysis
	Comments	MMRM Model: Percentage change in BMD = treatment+baseline+pooled site+visit+treatment*visit interaction. Repeat measure occurred at each visit.
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-7.50
	Confidence Interval	(2-Sided) 90%; -8.856 to -6.151
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.818
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 50 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	p-value for change in BMD at 12 months
	Method	Mixed Models Analysis
	Comments	MMRM Model: Percentage change in BMD = treatment+baseline+pooled site+visit+treatment*visit interaction. Repeat measure occurred at each visit.
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-7.46
	Confidence Interval	(2-Sided) 90%; -8.835 to -6.091
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.830
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 80 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	p-value is for change in BMD at 12 months
	Method	Mixed Models Analysis
	Comments	MMRM Model: Percentage change in BMD = treatment+baseline+pooled site+visit+treatment*visit interaction. Repeat measure occurred at each visit.
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-6.19
	Confidence Interval	(2-Sided) 90%; -7.510 to -4.860
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.802
	Estimation Comments

4. Secondary Outcome

Title	Percent Change From Baseline in Procollagen Type 1 N-Terminal Propeptide (P1NP)
Description	Procollagen Type 1 N-Terminal Propeptide (P1NP) is a marker of bone formation.
Time Frame	Baseline, 1 Month, 3 Months, 6 Months, 12 Months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug. The intent-to-treat principle was applied.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 micrograms (mcg) teriparatide subcutaneously once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	52	53	51	62
1 month (n=49, 53, 49, 60)	112.47 (65.390)	19.29 (35.274)	27.78 (31.064)	42.06 (53.000)
3 months (n=50, 51, 49, 59)	174.88 (118.745)	35.68 (50.358)	53.53 (64.625)	116.34 (117.697)
6 months (n=48, 49, 48, 56)	284.89 (228.773)	62.99 (78.579)	93.82 (93.575)	221.28 (233.297)
12 months (n=47, 46, 43, 49)	232.41 (176.557)	72.17 (86.747)	97.14 (98.007)	178.02 (181.361)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 30 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 1 month.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 50 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 1 month.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 80 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 1 month.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 30 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 3 months.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 50 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 3 months.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 80 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 3 months.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 30 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 6 months.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 50 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 6 months.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 80 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 6 months.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 30 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 12 months.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 50 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 12 months.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 80 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.047
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 12 months.

5. Secondary Outcome

Title	Percent Change From Baseline of C-Terminal Telopeptide (CTX)
Description	C-terminal telopeptide is a marker of bone resorption.
Time Frame	Baseline, 1 Month, 3 Months, 6 Months, 12 Months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug. The intent-to-treat principle was applied.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 micrograms (mcg) teriparatide subcutaneously once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	52	53	51	62
1 month (n=49, 53, 49, 60)	20.57 (64.980)	8.05 (26.070)	13.35 (29.384)	21.66 (46.572)
3 months (n=50, 51, 49, 59)	87.78 (96.777)	30.66 (42.048)	42.40 (58.620)	90.36 (103.367)
6 months (n=48, 49, 48, 56)	123.36 (128.832)	37.36 (52.875)	68.63 (71.059)	127.81 (152.725)
12 months (n=47, 46, 43, 49)	97.52 (109.981)	37.75 (58.035)	61.25 (60.862)	114.11 (157.485)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 30 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.822
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 1 month.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 50 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.406
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 1 month.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 80 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.312
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 1 month.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 30 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 3 months.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 50 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 3 months.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 80 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.952
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 3 months.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 30 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 6 months.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 50 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 6 months.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 80 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.997
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 6 months.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 30 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 12 months.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 50 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.112
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 12 months.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 80 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.988
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 12 months.

6. Secondary Outcome

Title	Percent Change From Baseline in Serum Procollagen Type 1 C-Propeptide (P1CP) at 1 Month
Description	Procollagen Type 1 N-Terminal Propeptide (P1NP) is a marker of bone formation.
Time Frame	Baseline, 1 Month

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug. The intent-to-treat principle was applied.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 micrograms (mcg) teriparatide subcutaneously once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	49	53	48	59
Median (Standard Deviation) [percentage change in P1CP]	80.10 (85.421)	4.63 (29.694)	12.30 (30.153)	23.84 (44.813)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 30 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 1 month.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 50 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 1 month.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	20 Mcg Subcutaneous Teriparatide, 80 Mcg Transdermal Teriparatide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments	Pairwise comparison p-value at 1 month.

7. Secondary Outcome

Title	Convenience/Ease of Use Questionnaire (CEUQ)
Description	CEUQ consists of 5 sections and 16 questions using a 5-point Likert scale designed to collect measures for ease of use (S1), convenience of use (S2), confidence of use (S3), fear of use (S4), and overall satisfaction with therapy (S5). CEUQ is not a validated instrument.
Time Frame	baseline up to 12 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had CEUQ assessment. Last observation was carried forward, unless the last observation was also the first completed questionnaire.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	55	54	51	62
S1-Stronly Disagree	0 0%	0 0%	0 0%	0 0%
S1-Somewhat Disagree	0 0%	0 0%	0 0%	0 0%
S1-Neutral	0 0%	0 0%	1 1.9%	0 0%
S1-Somewhat Agree	11 19.3%	9 16.1%	8 14.8%	10 15.6%
S1-Strongly Agree	44 77.2%	45 80.4%	42 77.8%	52 81.3%
S2-Strongly Disagree	0 0%	0 0%	0 0%	0 0%
S2-Somewhat Disagree	0 0%	0 0%	0 0%	0 0%
S2-Neutral	1 1.8%	1 1.8%	1 1.9%	0 0%
S2-Somewhat Agree	11 19.3%	12 21.4%	9 16.7%	12 18.8%
S2-Strongly Agree	43 75.4%	41 73.2%	41 75.9%	50 78.1%
S3-Not Confident	0 0%	0 0%	1 1.9%	0 0%
S3-Somewhat Not Confident	0 0%	1 1.8%	0 0%	1 1.6%
S3-Neutral	0 0%	0 0%	3 5.6%	4 6.3%
S3-Somewhat Confident	13 22.8%	15 26.8%	11 20.4%	17 26.6%
S3-Very Confident	42 73.7%	38 67.9%	36 66.7%	40 62.5%
S4-Extremely Fearful	0 0%	0 0%	1 1.9%	0 0%
S4-Somewhat Fearful	1 1.8%	1 1.8%	0 0%	1 1.6%
S4-Neutral	1 1.8%	0 0%	1 1.9%	0 0%
S4-Somewhat Not Fearful	9 15.8%	16 28.6%	9 16.7%	13 20.3%
S4-Not Fearful	44 77.2%	37 66.1%	40 74.1%	48 75%
S5-Very Dissatisfied	0 0%	0 0%	0 0%	0 0%
S5-Somewhat Dissatisfied	0 0%	1 1.8%	1 1.9%	0 0%
S5-Neutral	1 1.8%	0 0%	2 3.7%	1 1.6%
S5-Somewhat Satisfied	10 17.5%	13 23.2%	10 18.5%	18 28.1%
S5-Very Satisfied	44 77.2%	40 71.4%	38 70.4%	43 67.2%

8. Secondary Outcome

Title	Change in Serum Calcium With and Without Adjustments for Serum Albumin From Predose to After 4 and 6 Hours
Description	Serum calcium adjusted for serum albumin levels is calculated using the following formula: Total Calcium + [(40 - albumin) x 0.02]. Analysis for serum calcium and albumin adjusted serum calcium were collected at predose, 4 hours (h) post-dose (PD) and 6 h PD at baseline and 12 months (mon).
Time Frame	Baseline, 12 Months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had serum calcium measurements or adjusted serum calcium measurements at the indicated timepoint.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	57	56	54	64
Baseline- predose; no adjustment (n=54,53,51,62)	2.391 (0.0776)	2.362 (0.0933)	2.389 (0.0921)	2.392 (0.0915)
Baseline- 4 h PD; no adjustment (n=55,53,51,63)	2.432 (0.1191)	2.358 (0.1315)	2.403 (0.1160)	2.393 (0.1113)
Baseline- 6 h PD; no adjustment (n=52,51,48,59)	2.440 (0.1159)	2.369 (0.0789)	2.400 (0.1167)	2.397 (0.1048)
12 mon-predose; no adjustment (n=52,47,45,50)	2.463 (0.1243)	2.427 (0.0977)	2.427 (0.0842)	2.432 (0.0937)
12 mon-4 h PD; no adjustment (n=51,46,44,51)	2.516 (0.1815)	2.428 (0.1024)	2.430 (0.1199)	2.464 (0.1042)
12 mon-6 h PD; no adjustment (n=50,45,44,51)	2.532 (0.1429)	2.426 (0.0866)	2.443 (0.0997)	2.467 (0.0959)
baseline-predose albumin adjusted (n=53,53,50,60)	2.363 (0.0811)	2.341 (0.0949)	2.376 (0.0807)	2.373 (0.0809)
baseline-4 h PD; albumin adjusted (n=52,52,50,61)	2.418 (0.1099)	2.348 (0.1283)	2.403 (0.0928)	2.386 (0.1045)
baseline-6 h PD; albumin adjusted (n=49,50,47,57)	2.423 (0.1100)	2.363 (0.0727)	2.404 (0.0908)	2.394 (0.0934)
12 mon- predose albumin adjusted (n=52,47,45,50)	2.461 (0.0998)	2.432 (0.0806)	2.449 (0.0861)	2.442 (0.0840)
12 mon- 4 h PD; albumin adjusted (n=51,46,44,51)	2.523 (0.1680)	2.438 (0.1022)	2.458 (0.1012)	2.482 (0.0962)
12 mon-6 h PD; albumin adjusted (n=52,47,45,50)	2.547 (0.1236)	2.443 (0.0838)	2.481 (0.1044)	2.483 (0.1348)

9. Secondary Outcome

Title	Change From Baseline in Urine Calcium Excretion at 6 and 12 Months
Time Frame	Baseline, 6 Months, 12 Months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had urine calcium measurements at the indicated timepoint.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	57	56	54	64
Baseline	4.45 (1.851)	4.21 (1.766)	4.26 (1.673)	4.24 (1.876)
6 months (n=54, 50, 49, 56)	2.02 (4.122)	0.70 (3.467)	1.20 (2.768)	1.35 (2.360)
12 months (n=51, 47, 41, 51)	5.25 (3.694)	4.97 (2.192)	4.80 (2.738)	4.51 (2.770)

10. Secondary Outcome

Title	Change From Pre-dose and Postdose Supine and Standing SBP and DBP at Baseline (BL) and 12 Months (Mon)
Description	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) measured at pre-dose and 30 minutes (min) and 2 hours (hr) post-dose in both the supine and standing position.
Time Frame	Pre-Dose, 30 minutes, 2 hours Post-Dose at Baseline and 12 Months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had predose and postdose blood pressure measurements at the indicated timepoint and body position.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	57	56	54	64
BL, supine, SBP, 30 min (n=56,54,51,62)	-0.6 (10.71)	2.0 (10.25)	-1.0 (11.59)	-0.8 (10.77)
BL, supine, SBP, 2 h (n=56,56,53,63)	-0.3 (13.06)	-0.9 (10.97)	-3.5 (9.97)	-0.6 (12.91)
BL, supine, DBP, 30 min (n=56,54,51,62)	-1.9 (7.63)	1.4 (7.59)	-2.5 (7.50)	-1.1 (7.17)
BL, supine, DBP, 2 h (n=56,56,53,63)	-2.1 (7.59)	-0.8 (8.51)	-3.6 (7.02)	-1.6 (7.67)
12mon, supine, SBP, 30min (n=51,47,44,51)	0.8 (8.52)	-2.2 (7.47)	-1.1 (8.87)	-2.0 (9.82)
12mon, supine, SBP, 2 h (n=51,47,44,51)	-0.2 (10.71)	-1.8 (11.19)	-2.5 (9.54)	-1.9 (10.87)
12mon, supine, DBP, 30min (n=52,48,45,51)	-1.8 (7.14)	-1.8 (6.08)	-2.1 (6.77)	-1.2 (7.25)
12mon, supine, DBP, 2 h (n=51,47,44,51)	-1.3 (6.94)	-3.3 (7.79)	-1.3 (6.79)	-2.0 (8.59)
BL, standing, SBP, 30 min (n=56,54,51,62)	-1.3 (9.38)	2.5 (8.93)	-0.6 (10.65)	-0.5 (10.04)
BL, standing, SBP, 2 h (n=56,56,53,64)	-1.7 (11.57)	-1.6 (11.03)	-3.8 (10.96)	0.0 (12.11)
BL, standing, DBP, 30 min (n=56,54,51,62)	-2.3 (6.56)	0.2 (8.18)	-1.2 (8.34)	-1.2 (7.80)
BL, standing, DBP, 2 h (n=56,56,53,64)	-2.3 (7.55)	-2.1 (7.80)	-1.1 (7.25)	-1.7 (8.84)
12mon, standing, SBP, 30min(n=51,47,44,51)	-0.6 (10.55)	-0.9 (8.41)	0.5 (8.68)	-0.8 (8.72)
12mon, standing, SBP, 2 h (n=51,47,44,51)	-0.1 (11.86)	-0.4 (7.64)	-1.3 (12.97)	-0.9 (10.24)
12mon, standing, DBP, 30 min(n=51,47,44,51	-1.8 (7.12)	-2.4 (6.04)	-3.5 (8.09)	1.4 (7.75)
12mon, standing, DBP, 2 h (n=51,47,44,51)	1.1 (6.93)	-2.0 (7.35)	-1.9 (7.70)	0.1 (7.44)

11. Secondary Outcome

Title	Change From Pre-dose to Postdose in Supine and Standing Heart Rate at Baseline (BL) and 12 Months (Mon).
Time Frame	Pre-dose, 30 minutes, 2 hours at Baseline and 12 Months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had predose and postdose heart rate measurements at the indicated timepoint and body position.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 mcg teriparatide subcutaneously once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	57	56	54	64
BL, supine, 30 min (n=56,54,51,62)	1.8 (5.66)	1.7 (5.96)	-0.8 (7.21)	-0.6 (6.50)
BL, supine, 2 h (n=56,56,53,63)	1.5 (8.01)	0.9 (5.61)	-0.8 (8.49)	-0.4 (6.90)
BL, standing, 30 min (n=56,54,51,62)	1.6 (6.41)	-1.0 (7.36)	0.7 (6.68)	-1.2 (7.61)
BL, standing, 2 h (n=56,56,53,64)	1.0 (8.03)	-0.8 (8.51)	0.5 (6.51)	-1.0 (8.05)
12 mon, supine, 30 min (n=51,47,44,51)	2.5 (4.81)	1.4 (4.74)	-0.1 (4.06)	-0.2 (5.22)
12 mon, supine, 2 h (n=51,47,44,51)	1.6 (6.74)	1.1 (6.60)	-0.3 (5.43)	-0.8 (6.69)
12 mon, standing, 30 min (n=51,47,44,51)	1.2 (7.35)	0.0 (5.28)	-0.7 (5.97)	-0.4 (6.90)
12 mon, standing, 2 h (n=51,47,44,51)	0.9 (9.03)	0.1 (7.36)	-0.4 (7.03)	-0.7 (7.72)

12. Secondary Outcome

Title	Number of Participants With Parathyroid Hormone (PTH) Specific Antibody Levels
Description	Participants were tested for anti-recombinant teriparatide and anti-synthetic teriparatide titers. Either none were detected (ND) or antibodies were determined to be present if the teriparatide specific antibody titers were at least 1:8 (titer 1:8).
Time Frame	Baseline and 1, 3, 12, and 13 Months (mon)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had antibody results.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	57	56	54	64
Baseline: anti-recombinant ND (n=57, 54, 53, 64)	57 100%	54 96.4%	52 96.3%	64 100%
Baseline:anti-recombinant titer 1:8(n=57,54,53,64)	0 0%	0 0%	1 1.9%	0 0%
1 mon:anti-recombinant ND (n=54,54,51,62)	54 94.7%	54 96.4%	51 94.4%	62 96.9%
1 mon:anti-recombinant titer 1:8 (n=54,54,51,62	0 0%	0 0%	0 0%	0 0%
3 mon:anti-recombinant ND (n=55,52,51,61)	55 96.5%	52 92.9%	50 92.6%	61 95.3%
3 mon:anti-recombinant titer 1:8 (n=55,52,51,6	0 0%	0 0%	1 1.9%	0 0%
12 mon:anti-recombinant ND (n=52,48,45,51)	52 91.2%	48 85.7%	44 81.5%	51 79.7%
12 mon:anti-recombinant titer 1:8 (n=52,48,45,51)	0 0%	0 0%	1 1.9%	0 0%
13 mon:anti-recombinant ND (n=50,46,44,50)	50 87.7%	46 82.1%	43 79.6%	50 78.1%
13 mon:anti-recombinant titer 1:8 (n=50,46,44,50)	0 0%	0 0%	1 1.9%	0 0%
Baseline:anti-synthetic ND (n=57,54,53,64)	57 100%	54 96.4%	52 96.3%	64 100%
Baseline:anti-synthetic titer 1:8 (n=57,54,53,64)	0 0%	0 0%	1 1.9%	0 0%
1 mon:anti-synthetic ND (N=54,54,51,62)	54 94.7%	54 96.4%	50 92.6%	62 96.9%
1 mon:anti-synthetic titer 1:8 (N=54,54,51,62)	0 0%	0 0%	1 1.9%	0 0%
3 mon:anti-synthetic ND (n=55,52,51,61)	55 96.5%	52 92.9%	50 92.6%	61 95.3%
3 mon:anti-synthetic titer 1:8 (n=55,52,51,61)	0 0%	0 0%	1 1.9%	0 0%
12 mon:anti-synthetic ND (n=52,48,45,51)	52 91.2%	48 85.7%	44 81.5%	51 79.7%
12 mon:anti-synthetic titer 18 (n=52,48,45,51)	0 0%	0 0%	1 1.9%	0 0%
13 mon:anti-synthetic ND (n=50,46,44,50)	50 87.7%	46 82.1%	43 79.6%	50 78.1%
13 mon:anti-synthetic titer 1:8 (n=50,46,44,50)	0 0%	0 0%	1 1.9%	0 0%

13. Secondary Outcome

Title	Pharmacokinetics Parameters: Area Under the Curve (AUC)
Description	Due to high intra-subject variability, data was not analyzed for this outcome measure.
Time Frame	Baseline, 1 Month, 3 Months, and 12 Months

Outcome Measure Data

Analysis Population Description

Due to high intra-subject variability, zero participants were analyzed on this outcome measure.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	0	0	0	0

14. Secondary Outcome

Title	Pharmacokinetics Parameters: Maximal Concentration (Cmax)
Description	Due to high intra-subject variability, data was not analyzed for this outcome measure.
Time Frame	Baseline, 1 Month, 3 Months, 12 Months

Outcome Measure Data

Analysis Population Description

Due to high intra-subject variability, zero participants were analyzed for this outcome measure.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	0	0	0	0

15. Secondary Outcome

Title	DRAIZE Edema Assessment at Baseline Through 13 Month Follow-up
Description	Severity of edema was categorized based on a 5 point scale: 0=no edema, 4=severe edema (defined as an area raised more than 1 millimeter and extending beyond area of exposure)
Time Frame	13 Month follow-up

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had edema measurements at 13 months.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	41	39	39	43
0=no edema	41 71.9%	39 69.6%	39 72.2%	43 67.2%
1=very slight edema to 4=severe edema	0 0%	0 0%	0 0%	0 0%

16. Secondary Outcome

Title	DRAIZE Erythema Assessment at Baseline Through 13 Month Follow-up
Description	Severity of erythema was categorized based on a 5 point scale: 0=no erythema, 4=severe erythema (defined as beet red to eschar)
Time Frame	13 Month follow-up

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had erythema measurements at 13 months.

Arm/Group Title	20 Mcg Subcutaneous Teriparatide	30 Mcg Transdermal Teriparatide	50 Mcg Transdermal Teriparatide	80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.	Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.	Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Measure Participants	41	39	39	43
0=no erythema	41 71.9%	39 69.6%	39 72.2%	43 67.2%
1=very slight erythema to 4=severe erythema	0 0%	0 0%	0 0%	0 0%

Adverse Events

Arm/Group Title	20 Mcg Subcutaneous Teriparatide		30 Mcg Transdermal Teriparatide		50 Mcg Transdermal Teriparatide		80 Mcg Transdermal Teriparatide
Arm/Group Description	Received 20 microgram (mcg) teriparatide subcutaneously (injected) once daily in an unblinded manner.		Received 30 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.		Received 50 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.		Received 80 mcg teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
All Cause Mortality
	20 Mcg Subcutaneous Teriparatide		30 Mcg Transdermal Teriparatide		50 Mcg Transdermal Teriparatide		80 Mcg Transdermal Teriparatide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	20 Mcg Subcutaneous Teriparatide		30 Mcg Transdermal Teriparatide		50 Mcg Transdermal Teriparatide		80 Mcg Transdermal Teriparatide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/57 (3.5%)		2/56 (3.6%)		1/54 (1.9%)		5/64 (7.8%)
Blood and lymphatic system disorders
Haemorrhagic anaemia	0/57 (0%)	0	0/56 (0%)	0	0/54 (0%)	0	1/64 (1.6%)	1
Gastrointestinal disorders
Colonic polyp	0/57 (0%)	0	0/56 (0%)	0	0/54 (0%)	0	1/64 (1.6%)	1
Diverticulum intestinal	0/57 (0%)	0	0/56 (0%)	0	0/54 (0%)	0	1/64 (1.6%)	1
Haemorrhoids	0/57 (0%)	0	0/56 (0%)	0	0/54 (0%)	0	1/64 (1.6%)	1
Infections and infestations
Lobar pneumonia	0/57 (0%)	0	1/56 (1.8%)	1	0/54 (0%)	0	0/64 (0%)	0
Injury, poisoning and procedural complications
Hip fracture	0/57 (0%)	0	0/56 (0%)	0	0/54 (0%)	0	1/64 (1.6%)	1
Humerus fracture	0/57 (0%)	0	0/56 (0%)	0	1/54 (1.9%)	1	0/64 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/57 (0%)	0	1/56 (1.8%)	2	0/54 (0%)	0	0/64 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/57 (0%)	0	0/56 (0%)	0	0/54 (0%)	0	1/64 (1.6%)	1
Breast cancer	2/57 (3.5%)	2	0/56 (0%)	0	0/54 (0%)	0	0/64 (0%)	0
Metastatic neoplasm	0/57 (0%)	0	0/56 (0%)	0	0/54 (0%)	0	1/64 (1.6%)	1
Nervous system disorders
Cerebral haemorrhage	0/57 (0%)	0	0/56 (0%)	0	0/54 (0%)	0	1/64 (1.6%)	1
Other (Not Including Serious) Adverse Events
	20 Mcg Subcutaneous Teriparatide		30 Mcg Transdermal Teriparatide		50 Mcg Transdermal Teriparatide		80 Mcg Transdermal Teriparatide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/57 (52.6%)		33/56 (58.9%)		30/54 (55.6%)		39/64 (60.9%)
Blood and lymphatic system disorders
Anaemia	0/57 (0%)	0	2/56 (3.6%)	2	1/54 (1.9%)	1	0/64 (0%)	0
Ear and labyrinth disorders
Ear pain	2/57 (3.5%)	2	0/56 (0%)	0	1/54 (1.9%)	1	0/64 (0%)	0
Endocrine disorders
Hypothyroidism	0/57 (0%)	0	2/56 (3.6%)	2	1/54 (1.9%)	1	0/64 (0%)	0
Eye disorders
Cataract	1/57 (1.8%)	1	1/56 (1.8%)	1	2/54 (3.7%)	2	0/64 (0%)	0
Conjunctivitis	1/57 (1.8%)	1	2/56 (3.6%)	2	0/54 (0%)	0	1/64 (1.6%)	1
Gastrointestinal disorders
Abdominal distension	1/57 (1.8%)	1	0/56 (0%)	0	0/54 (0%)	0	2/64 (3.1%)	2
Abdominal pain upper	0/57 (0%)	0	2/56 (3.6%)	2	0/54 (0%)	0	0/64 (0%)	0
Constipation	1/57 (1.8%)	1	1/56 (1.8%)	1	1/54 (1.9%)	2	2/64 (3.1%)	2
Diarrhoea	1/57 (1.8%)	1	2/56 (3.6%)	2	2/54 (3.7%)	2	1/64 (1.6%)	1
Dyspepsia	2/57 (3.5%)	2	0/56 (0%)	0	0/54 (0%)	0	1/64 (1.6%)	2
Gastritis	0/57 (0%)	0	0/56 (0%)	0	2/54 (3.7%)	2	0/64 (0%)	0
Gastrooesophageal reflux disease	0/57 (0%)	0	2/56 (3.6%)	2	0/54 (0%)	0	0/64 (0%)	0
Nausea	1/57 (1.8%)	1	0/56 (0%)	0	0/54 (0%)	0	4/64 (6.3%)	5
General disorders
Application site discolouration	0/57 (0%)	0	2/56 (3.6%)	2	1/54 (1.9%)	1	1/64 (1.6%)	1
Infections and infestations
Bronchitis	3/57 (5.3%)	4	1/56 (1.8%)	1	1/54 (1.9%)	1	2/64 (3.1%)	2
Cystitis	0/57 (0%)	0	0/56 (0%)	0	0/54 (0%)	0	2/64 (3.1%)	3
Gastroenteritis	1/57 (1.8%)	1	2/56 (3.6%)	2	1/54 (1.9%)	1	1/64 (1.6%)	1
Influenza	3/57 (5.3%)	3	3/56 (5.4%)	3	1/54 (1.9%)	1	5/64 (7.8%)	5
Nasopharyngitis	2/57 (3.5%)	2	0/56 (0%)	0	2/54 (3.7%)	2	1/64 (1.6%)	1
Pharyngitis	0/57 (0%)	0	1/56 (1.8%)	1	2/54 (3.7%)	2	2/64 (3.1%)	2
Pneumonia	1/57 (1.8%)	1	0/56 (0%)	0	0/54 (0%)	0	2/64 (3.1%)	2
Urinary tract infection	3/57 (5.3%)	3	1/56 (1.8%)	1	2/54 (3.7%)	2	1/64 (1.6%)	1
Viral infection	2/57 (3.5%)	2	2/56 (3.6%)	2	1/54 (1.9%)	1	0/64 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/57 (0%)	0	0/56 (0%)	0	0/54 (0%)	0	2/64 (3.1%)	2
Fall	0/57 (0%)	0	2/56 (3.6%)	2	0/54 (0%)	0	1/64 (1.6%)	1
Radius fracture	4/57 (7%)	4	0/56 (0%)	0	0/54 (0%)	0	0/64 (0%)	0
Subcutaneous haematoma	3/57 (5.3%)	4	0/56 (0%)	0	0/54 (0%)	0	0/64 (0%)	0
Metabolism and nutrition disorders
Hypercalcaemia	1/57 (1.8%)	1	0/56 (0%)	0	0/54 (0%)	0	2/64 (3.1%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	1/57 (1.8%)	1	4/56 (7.1%)	4	1/54 (1.9%)	1	3/64 (4.7%)	3
Back pain	0/57 (0%)	0	1/56 (1.8%)	2	1/54 (1.9%)	2	3/64 (4.7%)	3
Muscle spasms	1/57 (1.8%)	1	0/56 (0%)	0	3/54 (5.6%)	3	2/64 (3.1%)	2
Musculoskeletal pain	2/57 (3.5%)	2	1/56 (1.8%)	2	1/54 (1.9%)	1	0/64 (0%)	0
Myalgia	1/57 (1.8%)	2	1/56 (1.8%)	1	0/54 (0%)	0	2/64 (3.1%)	2
Osteoarthritis	0/57 (0%)	0	0/56 (0%)	0	2/54 (3.7%)	2	1/64 (1.6%)	1
Pain in extremity	1/57 (1.8%)	1	0/56 (0%)	0	1/54 (1.9%)	1	2/64 (3.1%)	2
Nervous system disorders
Paraesthesia	1/57 (1.8%)	1	1/56 (1.8%)	1	2/54 (3.7%)	2	0/64 (0%)	0
Sciatica	0/57 (0%)	0	0/56 (0%)	0	0/54 (0%)	0	2/64 (3.1%)	2
Psychiatric disorders
Depression	1/57 (1.8%)	1	2/56 (3.6%)	2	2/54 (3.7%)	2	0/64 (0%)	0
Insomnia	0/57 (0%)	0	0/56 (0%)	0	3/54 (5.6%)	3	0/64 (0%)	0
Renal and urinary disorders
Hypercalciuria	2/57 (3.5%)	2	1/56 (1.8%)	1	5/54 (9.3%)	5	6/64 (9.4%)	6
Skin and subcutaneous tissue disorders
Pruritus	0/57 (0%)	0	0/56 (0%)	0	2/54 (3.7%)	2	0/64 (0%)	0
Vascular disorders
Hypertension	2/57 (3.5%)	2	2/56 (3.6%)	2	1/54 (1.9%)	1	3/64 (4.7%)	4
Intra-abdominal haematoma	3/57 (5.3%)	3	0/56 (0%)	0	0/54 (0%)	0	0/64 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.