OLES: Open Label Extension Study of PREOS

Sponsor

Shire (Industry)

Overall Status

Completed

CT.gov ID

NCT00172133

Collaborator

(none)

1,683

Enrollment

132

Locations

Arm

41.9

Actual Duration (Months)

12.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an Open Label Extension Study (OLES) for patients who participated in the 18 month double-blind, placebo-controlled, Phase III trial (Protocol ALX1 11 93001 the TOP Study) studying the effect of ALX1-11, recombinant human parathyroid hormone, rhPTH(1-84), on vertebral fracture incidence. The primary objective of this study is to evaluate the safety of continued dosing with ALX1-11, up to a maximum of 24 months, in postmenopausal osteoporotic women who participated in Protocol ALX1 11 93001.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis	Drug: ALX1-11 (drug)	Phase 3

Detailed Description

Effects of ALX1-11 on bone mineral density (BMD) have been documented in a dose-finding Phase II clinical trial in osteoporotic postmenopausal women, supplemented with calcium and Vitamin D3 but without any other treatment for osteoporosis. The anabolic effects of ALX1-11 in the lumbar vertebrae were statistically significant after the 12-month treatment period and more pronounced than any approved therapy. Additionally, animal studies have shown that the new bone formed by treatment with ALX1 11 is of good quality both histologically and biomechanically.

The primary objective of this OLES is to evaluate the safety of continued dosing with ALX1-11, up to a maximum of 24 months, in postmenopausal osteoporotic women who participated in Protocol ALX1-11-93001. A secondary objective is to assess the change in vertebral BMD and compare the changes observed in patients who received ALX1-11 or placebo in Protocol ALX1-11-93001.

Patients will receive 100 µg/day of ALX1-11 daily via subcutaneous injection in this study. Patients should continue the study drug dosing frequency they were following at the end of Protocol ALX1-11-93001.

To enhance their safety, all patients will continue to take their daily supplements of 700 mg calcium and 400 IU Vitamin D3 prior to and during this OLES. Patients whose calcium supplement was discontinued during Protocol ALX1-11-93001 should maintain that discontinuation during this OLES. However upon completion of ALX1-11 dosing in the OLES, oral calcium supplement at a dose of 700 mg each morning should be restarted and maintained for the remainder of the OLES. Additional supplemental calcium and/or Vitamin D3 will not be permitted. A daily multivitamin supplement may be taken during the study. However, the multivitamin must contain no more than 200 mg/day calcium and 400 IU/day Vitamin D3. Patients will be monitored for the development of hypercalcemia and/or hypercalciuria and managed as described in Appendices 4 and 5.

There will be a stopping rule in this OLES. Any patient who reaches a BMD T score of -0.5 or above, at the site or sites (vertebral, total hip, or femoral neck) that were used in the qualification of the patient for Protocol ALX1 11-93001, will stop ALX1-11 treatment. The patient must continue on calcium and Vitamin D3 and be followed for the remainder of this 18-month OLES. At the time of discontinuation, the patient must complete the Month 18 evaluations (Appendix 1A or 1B).

The Clinical Advisory Board (CAB) used in Protocol ALX1-11-93001 will be involved in reviewing any patient issues that arise in this OLES. This group will provide not only continuity of care for all the patients, but also enhanced and consistent safety monitoring for patients participating in the OLES.

Study Design

Study Type:

Interventional

Actual Enrollment :

1683 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An 18-Month Open Label Extension Study (OLES) of the Safety and Efficacy of Recombinant Human Parathyroid Hormone, rhPTH(1-84), ALX1-11, in Women With Postmenopausal Osteoporosis Who Participated in Protocol ALX1-11-93001 (TOP Study)

Actual Study Start Date :

Oct 16, 2001

Actual Primary Completion Date :

Apr 13, 2005

Actual Study Completion Date :

Apr 13, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 All patients entering the study will receive 100mcg daily for up to 6 months, making their total exposure 24 months	Drug: ALX1-11 (drug) 100 mcg PTH(1-84) injected subcutaneously daily in either the thrigh and abdomen. Other Names: PREOS

Arm

Intervention/Treatment

Experimental: 1

All patients entering the study will receive 100mcg daily for up to 6 months, making their total exposure 24 months

Drug: ALX1-11 (drug)

100 mcg PTH(1-84) injected subcutaneously daily in either the thrigh and abdomen.

Other Names:

PREOS

Outcome Measures

Primary Outcome Measures

To evaluate the safety of continued dosing with ALX1-11, up to a maximum of 24 months, in postmenopausal osteoporotic women who participated in Protocol ALX1-11-93001 (TOP). [24 months of treatment]

Secondary Outcome Measures

To evaluate the continued efficacy of once-daily treatment with ALX1-11 for maintaining increases in BMD and other measures of bone quality and strength. [24 months of treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women who completed 18 months of treatment in Protocol ALX1-11-93001; or
Women prematurely discontinued from Protocol ALX1-11-93001 who want to participate in OLES for the events listed below must have their clinical course reviewed and approved by the CAB for enrollment into the OLES:
Clinical or incident lumbar vertebral fractures as assessed by the central imaging organization
Clinical or incident hip fracture
Confirmed bone loss at A/P lumbar vertebra or total hip or femoral neck as assessed by the central imaging organization
Body weight below 40 kg
Development of an exclusion criterion in Protocol ALX1-11-93001
It must be accepted by patients whose clinical courses are reviewed by the CAB that participation in OLES may require additional tests at baseline and/or during the study to ensure their utmost safety.
Women with the ability to self-administer a daily injection or have a designee who will give the injections;
Women who are capable of understanding and giving written, voluntary informed consent before the start of open-label dosing with ALX1-11.

Exclusion Criteria:

A. History or Concurrent Illness:

Disorders of Immunity Endocrine system Gastrointestinal system Kidney and collecting system Liver, biliary tract and pancreatic systems Musculoskeletal system

Patients with chronic, active joint disease requiring more than one intra-articular injection every 6 months Neoplasia
Patients who have had squamous or basal cell carcinoma of the skin may enter this study if:

The lesion(s) were fully resected with clear margins described in a written report by a pathologist, and
The patient has had no recurrence of lesions for at least one year from the time of the original resection.

Nervous system Vascular, respiratory and cardiac system *Significant diseases or disorders are determined by history, physical exam or laboratory tests and judged by the Principal Investigator to be significant.

B. Concurrent Medication:

Patients may not use any of the following therapies while they are enrolled in this OLES without permission from the Sponsor and the PMO:

Tetracycline antibiotics for four weeks prior to bone biopsy
Any PTH analogs [e.g., rhPTH(1-84), PTH(1-34), PTHrP and analogs]
Fluoride
Strontium
Phenytoin for seizure control
Any investigational drug other than ALX1-11
Anabolic steroids or androgens
Active Vitamin D3 metabolites and analogs, e.g., calcitriol
Systemic corticosteroids, more than 5 mg/day prednisone or a systemic corticosteroid formulation equivalent to 5 mg/day prednisone

A patient who has been enrolled into the OLES and needs to receive an acute bolus of steroids (oral or injectable) for a self-limited illness may continue treatment in the study if the following requirements are met:
Exposure to steroids will be limited to no more than 30 consecutive days
The maximal dose of steroid (prednisone equivalent) must be limited to no more than 225 mg (7.5 mg each day for 30 days)
The illness is acute in nature and is not expected to recur during the remaining period of the study

Bisphosphonates, including investigational bisphosphonates
Calcitonin
Estrogen replacement therapy by oral, transdermal or intramuscular administration
SERM drugs, e.g., tamoxifen, raloxifene, Evista
Vaginal application of estrogen-containing creams unless the dose is:

conjugated estrogen or estradiol: maximum of 0.5 g twice each week (total of 1.0 g weekly)
Estrace (Ogen): maximum of 1.0 g twice each week (total of 2.0 g weekly)

Daily inhaled corticosteroid unless dose is equivalent to <1200 µg/day of beclomethasone
Cytostatics, e.g., azathioprine, recombinant human tumor necrosis fusion (Fc) protein, monoclonal antibody against tumor necrosis factor (e.g., remicade [infliximab]
Methotrexate

The antimetabolite, methotrexate, which interferes with DNA synthesis, repair and cellular replication should not be used by patients participating in this OLES.

In general, immunomodulatory agents with antiproliferative activity are not permitted as a concomitant medication in this OLES.
Intra-articular injections

Patients may receive a maximum of one intra-articular injection (ONE JOINT ONLY) every 6 months while participating in this OLES. The joint that is injected may be a different joint every 6 months. The dose of corticosteroid injected should not exceed the anti-inflammatory equivalent dose of Prednisone 40 mg suspension. The dose and volume should be adjusted downward as appropriate to the size of the joint.

Provera is an acceptable concomitant medication when used according to the label instructions

Patients may be enrolled in this OLES if they have been stabilized on the following therapy for the specified amount of time:

Thyroid Hormone (<0.1 mg/day thyroxine) therapy for at least 6 months If taking > 0.1 mg/day but < 0.2 mg/day, must have serum TSH level 1. > 0.1mU/L. Patients will be excluded if they are taking doses of > 0.2 mg/day.

However, if a patient has had a minimal change in L-thyroxine dose of < 0.025 mg/day within 6 months of the baseline visit, and has been on this new dose for at least 2 months, the patient may be enrolled in this study. The patient's history with L-thyroxine must be clearly documented in the source documents.
If a patient requires an increase in their thyroid replacement dose, as recommended by a physician who is caring for the patient, after enrollment in this OLES, the patient must have a TSH and T4 level within 3 months of the dose change to ensure the patient does not become hyperthyroid

Stable dosage of thiazide for at least 3 consecutive months

C. Laboratory Values and Physical Examination Findings:

Serum calcium greater than 10.7 mg/dL (2.66 mmol/L) at baseline will be managed as outlined in Appendix 4
Urinary calcium to creatinine ratio greater than or equal to 1 at baseline will be managed as outlined in Appendix 5
Elevated total serum alkaline phosphates (> 400 U/L) at baseline will be managed as outlined in Appendix 6 except as noted for Latin and South American countries.
Any other clinically significant abnormal value as judged by the investigator

D. Substance Abuse:

Alcohol and/or drug abuse

E. Compliance:

Suspected or confirmed poor compliance in completing clinical trial evaluations and/or clinical trial required questionnaires

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	'The University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	'Rheumatology Associates of North Alabama	Huntsville	Alabama	United States	35801
3	'Radiant Research - Phoenix North	Phoenix	Arizona	United States	85013
4	'Osteoporosis Medical Center	Beverly Hills	California	United States	90211
5	'East Bay Clinical Trial Center	Concord	California	United States	94520
6	'Loma Linda Osteoporosis Research Center	Loma Linda	California	United States	92354
7	Foundation for Osteoporosis Research	Oakland	California	United States	94612
8	'Desert Medical Advances	Palm Desert	California	United States	92260
9	'VA Palo Alto Health Care System	Palo Alto	California	United States	94304
10	'Boling Clinical Trials	Rancho Cucamonga	California	United States	91730
11	'S.D. Arthritis & Osteoporosis Medical Clinic	San Diego	California	United States	92120
12	'Radiant Research - San Diego	San Diego	California	United States	92123
13	'San Francisco General Hospital	San Francisco	California	United States	94110
14	'Longmont Medical Research Network	Longmont	Colorado	United States	80501
15	'Northeast Clinical Research, LLC	Hamden	Connecticut	United States	06518
16	'RASF - Clinical Research Center	Boca Raton	Florida	United States	33486
17	'The Center for Diabetes and Endocrine Care	Hollywood	Florida	United States	33021
18	'Florida Wellcare Alliance	Inverness	Florida	United States	34452
19	'Renstar Medical Group	Ocala	Florida	United States	34471
20	'The Arthritis Center	Palm Harbor	Florida	United States	34684
21	'The Centre for Arthritis and Rheumatic Diseases	South Miami	Florida	United States	33143
22	'Radiant Research - Stuart & LakeWorth	Stuart	Florida	United States	34996
23	'Palm Beach Research Center	West Palm Beach	Florida	United States	33409
24	'Radiant Research	Honolulu	Hawaii	United States	96814
25	'Intermountain Orthopaedics	Boise	Idaho	United States	83702
26	Rush-Prebyterian-St.Luke's Medical Center	Chicago	Illinois	United States	60612
27	'The University of Chicago	Chicago	Illinois	United States	60637
28	'University Hospital & Outpatient Center	Indianapolis	Indiana	United States	46202
29	'Mercy Arthritis and Osteoporosis Center	Des Moines	Iowa	United States	50322
30	'Wichita Clinic	Wichita	Kansas	United States	67208
31	'Ochsner Clinic	New Orleans	Louisiana	United States	70121
32	'Maine Center for Osteoporosis Research & Education	Bangor	Maine	United States	04401
33	'Bethesda Health Research Center	Bethesda	Maryland	United States	20817
34	'The Osteoporosis and Clinical Trials Center	Cumberland	Maryland	United States	21502
35	'Arthritis & Osteoporosis Center of Maryland	Frederick	Maryland	United States	21702
36	'The Center for Rheumatology and Bone Research	Wheaton	Maryland	United States	20902
37	'Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
38	'Michigan Bone & Mineral Clinic	Detroit	Michigan	United States	48236
39	'Desoto Family Medical Center	Olive Branch	Mississippi	United States	38654
40	'St. John's Medical Research Group	Springfield	Missouri	United States	65807
41	'Arthritis, Osteoporosis Muscle Skeletal Disease Center	Concord	New Hampshire	United States	03301
42	'Anderson and Collins Clinical Research Inc.	South Plainfield	New Jersey	United States	07080
43	'New Mexico Clinical Research and Osteoporosis Center	Albuquerque	New Mexico	United States	87106
44	'Lovelace Scientific Resources	Albuquerque	New Mexico	United States	87108
45	'College of Physicians and Surgeons, Columbia University	New York	New York	United States	10032
46	'Rochester Clinical Research Inc.	Rochester	New York	United States	14609
47	'Stony Brook Clinical Research Trials Center	Stony Brook	New York	United States	11794
48	'Physicians Clinical Research Services	White Plains	New York	United States	10605
49	'Duke University Medical Center	Durham	North Carolina	United States	27710
50	'Odyssey Research Services	Bismarck	North Dakota	United States	58501
51	Michael J. Lillestol	Fargo	North Dakota	United States	58103
52	'Altru Health Systems / Altru Research Center	Grand Forks	North Dakota	United States	58201
53	'Odyssey Research Services	Minot	North Dakota	United States	58701
54	'Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
55	'David R. Mandel M.D. Inc.	Mayfield	Ohio	United States	44143
56	'Oklahoma Center for Arthritis Therapy & Research, Inc.	Tulsa	Oklahoma	United States	74114
57	'Osteoporosis Center	Medford	Oregon	United States	97504
58	'Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
59	'Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19131
60	'University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
61	'Clinical Research Center of Reading LLP	West Reading	Pennsylvania	United States	19611
62	'Radiant Research	Wyomissing	Pennsylvania	United States	19610
63	'Rhode Island Hospital	Providence	Rhode Island	United States	02903
64	'Roger Williams Medical Center	Providence	Rhode Island	United States	02908
65	'Radiant Research	Anderson	South Carolina	United States	29621
66	'Columbia Arthritis Center, PA	Columbia	South Carolina	United States	29204
67	'Radiant Research	Greer	South Carolina	United States	29651
68	'Rapid City Medical Center	Rapid City	South Dakota	United States	57701
69	'Averna Research Institute	Sioux Falls	South Dakota	United States	57105
70	'Brown Clinic	Watertown	South Dakota	United States	57201
71	'Clinsearch	Chattanooga	Tennessee	United States	37404
72	'Radiant Research/Dallas	Dallas	Texas	United States	75235
73	'Breco Research Inc.	Houston	Texas	United States	77024
74	'Diabetes Center of the Southwest	Midland	Texas	United States	79705
75	'Diabetes & Glandular Disease Research Associates, P.A.	San Antonio	Texas	United States	78229
76	'Radiant Research San Antonio	San Antonio	Texas	United States	78229
77	'Salt Lake Women's Center	Sandy	Utah	United States	84070
78	'Fletcher Allan Health Center, UHC Campus 1	Burlington	Vermont	United States	05401
79	'Center for Arthritis and Diabetes	Newport News	Virginia	United States	23606
80	'National Clinical Research, Inc.	Richmond	Virginia	United States	23294
81	'MCV Physicians Program for Osteoporosis	Richmond	Virginia	United States	23298
82	'Osteoporosis Research Group	Seattle	Washington	United States	98105
83	'University of Wisconsin Medical Foundation	Madison	Wisconsin	United States	53792
84	'Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
85	'IDIM	Buenos Aires	BUE	Argentina	C1012AAR
86	'Centro Médico T.I.E.M.P.O	Buenos Aires	BUE	Argentina	C1117ABH
87	'Hospital Ramos Mejía	Buenos Aires	BUE	Argentina	C1221ADC
88	'Centro de Osteopatias Medicas	Capital Federal	CBA	Argentina	C1114AAI
89	'Universidade Federal do Paraná	Curitiba	PR	Brazil	80060
90	'Hospital Santa Casa de Misericórdia do Rio de Janeiro	'Rio de Janeiro	RJ	Brazil	20020
91	'Hospital do Servidor Público do Rio de Janeiro	Rio de Janeiro	RJ	Brazil	20221
92	'Universidade Federal de São Paulo	Sao Paulo	SP	Brazil	04038
93	'Instituto de Saúde e Bem Estar da Mulher	Sao Paulo	SP	Brazil	04062
94	'Hospital Heliópolis	Sao Paulo	SP	Brazil	04231
95	'Heritage Medical Research Clinic	Calgary	Alberta	Canada	'T2N 4N1
96	Osteoporosis Research Center	Vancouver	British Columbia	Canada	V5Z 2N6
97	'Manitoba Clinic	Winnipeg	Manitoba	Canada	'R3A 1M3
98	Charlton medical Centre	Hamilton	Ontario	Canada	L8N 1Y2
99	Rafat Faraawi	Kitchener	Ontario	Canada	N2M 5N6
100	'Centre for Activity and Aging	London	Ontario	Canada	'N6G 2M3
101	St. Joseph's Health Centre	London	Ontario	Canada	N6A 4V2
102	'Royal Victoria Hospital	Montreal	Ontario	Canada	'H3A 1A1
103	Oakville Bone Center	Oakville	Ontario	Canada	L6J 1X8
104	Ottawa Hospital	Ottawa	Ontario	Canada	'K1H 8L6
105	'Sunnybrook and Women's College Health Science Center	Toronto	Ontario	Canada	'M4N 3M5
106	'St. Michael's Hospital	Toronto	Ontario	Canada	'M5C 2T2
107	'Osteoporosis Research Program	Toronto	Ontario	Canada	'M5S 1B2
108	Jude F. Rodrigues	Windsor	Ontario	Canada	N8W 5L7
109	'Riverside Medical Centre	Charlottetown	Prince Edward Island	Canada	C1A 6A4
110	'Complexe Hospitalier de la Sagami	Chicoutimi	Quebec	Canada	G7H 5H6
111	'Hopital Maisonneuve-Rosemont	Montreal	Quebec	Canada	'H1T 2M4
112	'Centre de Recherche du CHUM - Hopital Saint-Luc	Montreal	Quebec	Canada	'H2X 1P1
113	Centre de recherche - CORQ	Sainte-Foy	Quebec	Canada	G1V 3M7
114	Novabyss Research Clinic	Sherbrooke	Quebec	Canada	J1J 2B8
115	'Saskatoon Osteoporosis Centre	'Saskatoon	Saskatchewan	Canada	'S7K 0H6
116	'Soroka Medical Center	Beer Sheva		Israel	84101
117	'Rambam Medical Center	Haifa		Israel	31096
118	'Lin Medical Center	Haifa		Israel	34162
119	'Hadassah University Hospital	Jerusalem		Israel	91240
120	'Chaim Sheba Medical Center	Ramat Gan		Israel	52621
121	'Lis Maternity Hospital	Tel Aviv		Israel
122	'Instituto Mexicano de Investigacion Clinica	Mexico	DF	Mexico	06700
123	'Hospital de Mexico	Mexico	DF	Mexico	11800
124	'Hospital Angeles de las Lomas	'Huixquilucan	Emex	Mexico	52763
125	'Hospital Aranda de la Parra	Leon	GTO	Mexico	37000
126	'OPD Hospital Civil de Guadalajara Dr. Juan I. Menchaca	Guadalajara	JAL	Mexico	44340
127	'Hospital Civil de Belem	Guadalajara	JAL	Mexico	44650
128	'Medica Monraz	Guadalajara	JAL	Mexico	44670
129	'Hospital Universitario de Monterrey	Monterrey Nuevo Leon		Mexico	64040
130	'Spitalul Clinic Judetean Cluj-Napoca	Cluj-Napoca		Romania	3400
131	'Scientific Center of Endocrinology of RAMS	Moscow		Russian Federation	117036
132	'Russian Academy for Advanced Medical Studies	Moscow		Russian Federation	125315