AMPLEX Ankle Fusion and Hindfoot

• Sponsor: Ferring Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03028415
• Collaborator: (none)
• Enrollment: 56
• Locations: 36
• Arms: 2
• Actual Duration (Months): 35.4
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To demonstrate that AMPLEX is non-inferior to autogenous bone graft (ABG) for bone fusion in a population indicated for single, double, or triple hindfoot arthrodesis or ankle arthrodesis surgery with supplemental graft material.

Condition or Disease	Intervention/Treatment	Phase
Arthrodesis Surgery Involving the Hindfoot or Ankle	Device: AMPLEX; Procedure: Autogenous Bone Graft (ABG)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Randomized, Pivotal Study Evaluating AMPLEX Compared To Autogenous Bone Graft in Subjects Indicated for Arthrodesis Surgery Involving the Hindfoot or Ankle
• Actual Study Start Date: Jul 28, 2017
• Actual Primary Completion Date: Jan 9, 2020
• Actual Study Completion Date: Jul 9, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMPLEX	Device: AMPLEX; A bone graft substitute
Active Comparator: Autogenous Bone Graft (ABG)	Procedure: Autogenous Bone Graft (ABG); Control material administered by surgical implant

Outcome Measures

Primary Outcome Measures

1. Proportion of Subjects Who Met All Five Criteria for Subject Performance Composite (SPC) Endpoint [At week 52]

   Proportion of subjects who met all the following criteria for the SPC endpoint at 52 weeks: 1. Improvement in pain on weight-bearing at fusion site (≥20 mm reduction from baseline on 100 mm visual analog scale [VAS]); 2. Absence of significant graft harvest site pain (<20 mm on 100 mm VAS); 3. Improvement in Foot and Ankle Ability Measure Activities of Daily Living subscale (FAAM-ADL) (≥8 points improvement from baseline); 4. Absence of device related or procedure related serious adverse events (up to week 52); 5. Absence of secondary surgical or nonsurgical interventions intended to promote fusion (up to week 52). The last observation carried forward was used for subjects with missing response status at 52 weeks.

Secondary Outcome Measures

1. Proportion of Subjects Achieving Computerized Tomography (CT) Radiographic Fusion Success [At week 52]

   Defined as ≥50% bone bridging across the joint space for the full complement of joints in the absence of secondary surgical or nonsurgical interventions intended to promote fusion. The last observation carried forward was used for subjects with missing response status at 52 weeks.

2. Proportion of Subjects Achieving CT Radiographic Fusion Success [At week 12]

   Defined as ≥50% bone bridging across the joint space for the full complement of joints in the absence of secondary surgical or nonsurgical interventions intended to promote fusion.

3. Proportion of Subjects Achieving CT Radiographic Fusion Success [At week 24]

   Defined as ≥50% bone bridging across the joint space for the full complement of joints in the absence of secondary surgical or nonsurgical interventions intended to promote fusion.

4. Proportion of Subjects With Change From Baseline in Pain on Weight-bearing at Fusion Site (>20 mm Reduction From Baseline on 100 mm VAS) [Baseline, and at week 12]

   Weight-bearing pain at the fusion site was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire. Subjects were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced, with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Improvement in pain on weight-bearing at the fusion site was defined as ≥ 20 mm reduction from baseline on 100 mm VAS, and is presented for this outcome measure.

5. Proportion of Subjects With Change From Baseline in Pain on Weight-bearing at Fusion Site (>20 mm Reduction From Baseline on 100 mm VAS) [Baseline, and at week 24]

   Weight-bearing pain at the fusion site was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire. Subjects were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced, with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Improvement in pain on weight-bearing at the fusion site was defined as ≥ 20 mm reduction from baseline on 100 mm VAS, and is presented for this outcome measure.

6. Proportion of Subjects With Change From Baseline in Pain on Weight-bearing at Fusion Site (>20 mm Reduction From Baseline on 100 mm VAS) [Baseline, and at week 52]

   Weight-bearing pain at the fusion site was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire. Subjects were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced, with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Improvement in pain on weight-bearing at the fusion site was defined as ≥ 20 mm reduction from baseline on 100 mm VAS, and is presented for this outcome measure.

7. Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS) [At week 2]

   Graft harvest site pain was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire, and was only assessed among subjects in the ABG group. Subjects in the ABG group were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Absence of significant graft harvest site pain was defined as <20 mm on 100 mm VAS, and is presented for this outcome measure.

8. Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS) [At week 6]

   Graft harvest site pain was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire, and was only assessed among subjects in the ABG group. Subjects in the ABG group were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Absence of significant graft harvest site pain was defined as <20 mm on 100 mm VAS, and is presented for this outcome measure.

9. Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS) [At week 12]

   Graft harvest site pain was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire, and was only assessed among subjects in the ABG group. Subjects in the ABG group were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Absence of significant graft harvest site pain was defined as <20 mm on 100 mm VAS, and is presented for this outcome measure.

10. Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS) [At week 24]

    Graft harvest site pain was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire, and was only assessed among subjects in the ABG group. Subjects in the ABG group were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Absence of significant graft harvest site pain was defined as <20 mm on 100 mm VAS, and is presented for this outcome measure.

11. Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS) [At week 52]

    Graft harvest site pain was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire, and was only assessed among subjects in the ABG group. Subjects in the ABG group were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Absence of significant graft harvest site pain was defined as <20 mm on 100 mm VAS, and is presented for this outcome measure.

12. Change From Baseline in FAAM-ADL [Baseline, and at week 12]

    Functional improvement was assessed using the Foot and Ankle Ability Measure Activities of Daily Living (FAAM-ADL) subscale, a subject self-assessment questionnaire that consists of 21 items pertaining to basic functional activities. Each item is scored on a 5 point Likert scale anchored by 4 (no difficulty at all) and 0 (unable to do). The total item subscale score ranges from 0 to 84, which are transformed to a scale of 0 to 100 as the final score. Higher scores represent a higher level of function, with 100 representing no dysfunction.

13. Change From Baseline in FAAM-ADL [Baseline, and at week 24]

    Functional improvement was assessed using the e Foot and Ankle Ability Measure Activities of Daily Living (FAAM-ADL) subscale, a subject self-assessment questionnaire that consists of 21 items pertaining to basic functional activities. Each item is scored on a 5 point Likert scale anchored by 4 (no difficulty at all) and 0 (unable to do). The total item subscale score ranges from 0 to 84, which are transformed to a scale of 0 to 100 as the final score. Higher scores represent a higher level of function, with 100 representing no dysfunction.

14. Change From Baseline in FAAM-ADL [Baseline, and at week 52]

    Functional improvement was assessed using the Foot and Ankle Ability Measure Activities of Daily Living (FAAM-ADL) subscale, a subject self-assessment questionnaire that consists of 21 items pertaining to basic functional activities. Each item is scored on a 5 point Likert scale anchored by 4 (no difficulty at all) and 0 (unable to do). The total item subscale score ranges from 0 to 84, which are transformed to a scale of 0 to 100 as the final score. Higher scores represent a higher level of function, with 100 representing no dysfunction.

15. Subject Performance Composite (SPC) Endpoint [At week 12]

    Proportion of subjects who met all the following criteria for the Subject Performance Composite (SPC) endpoint at 12 weeks: 1. Improvement in pain on weight-bearing at fusion site (≥20 mm reduction from baseline on 100 mm visual analog scale [VAS]); 2. Absence of significant graft harvest site pain (<20 mm on 100 mm VAS); 3. Improvement in Foot and Ankle Ability Measure Activities of Daily Living subscale (FAAM-ADL) (≥8 points improvement from baseline); 4. Absence of device related or procedure related serious adverse events (up to week 12); 5. Absence of secondary surgical or nonsurgical interventions intended to promote fusion (up to week 12).

16. Subject Performance Composite (SPC) Endpoint [At week 24]

    Proportion of subjects who met all the following criteria for the SPC endpoint at 24 weeks: 1. Improvement in pain on weight-bearing at fusion site (≥20 mm reduction from baseline on 100 mm visual analog scale [VAS]); 2. Absence of significant graft harvest site pain (<20 mm on 100 mm VAS); 3. Improvement in Foot and Ankle Ability Measure Activities of Daily Living subscale (FAAM-ADL) (≥8 points improvement from baseline); 4. Absence of device related or procedure related serious adverse events (up to week 24); 5. Absence of secondary surgical or nonsurgical interventions intended to promote fusion (up to week 24).

17. Change From Baseline in Short Form-12 (SF-12) [Baseline, and at week 24]

    The Short Form-12 (SF-12) Health Survey includes 12 questions from the SF-36 Health Survey. These include: 2 questions concerning physical functioning; 2 questions on role limitations because of physical health problems; 1 question on bodily pain; 1 question on general health perceptions; 1 question on vitality (energy/fatigue); 1 question on social functioning; 2 questions on role limitations because of emotional problems; and 2 questions on general mental health (psychological distress and psychological well-being). These eight domain scales were used to derive Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. All scores were calculated through scoring software. Domain scales and component summary scores ranged from 0 to 100, with a higher score considered better.

18. Change From Baseline in Short Form-12 (SF-12) [Baseline, and at week 52]

    The Short Form-12 (SF-12) Health Survey includes 12 questions from the SF-36 Health Survey. These include: 2 questions concerning physical functioning; 2 questions on role limitations because of physical health problems; 1 question on bodily pain; 1 question on general health perceptions; 1 question on vitality (energy/fatigue); 1 question on social functioning; 2 questions on role limitations because of emotional problems; and 2 questions on general mental health (psychological distress and psychological well-being). These eight domain scales were used to derive Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. All scores were calculated through scoring software. Domain scales and component summary scores ranged from 0 to 100, with a higher score considered better.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed written informed consent

• Indicated for ankle or hindfoot arthrodesis and require one of the following arthrodesis procedures:

Tibiotalar (ankle); Talocalcaneal (subtalar); Talonavicular; Calcaneocuboid; Double hindfoot (e.g., talonavicular and talocalcaneal joints); Triple hindfoot (subtalar, talonavicular and calcaneocuboid joints)

• Presents with pain on weight-bearing of at least 40 mm on a 100 mm VAS at the area indicated for arthrodesis

• Presents with at least one comorbid risk factors that warrant the use of supplemental autogenous bone or allograft:

Radiographic evidence of bone defect, deficit, subsidence or subchondral cyst; More than one joint to be fused; Involvement of other adjacent or nonadjacent joints; Large surface area; Intra-articular or extra-articular deformity; Post-traumatic arthritis; Diagnosis of osteoporosis

• The Investigator determines if the joint space(s) can be adequately filled with graft material (AMPLEX or ABG) according to the following parameters:

Single hindfoot joint fusion: up to 5 cm^{3; Double or triple hindfoot fusion: each individual joint up to 5 cm}3, but overall, not more than 10 cm3 for the full complement of joints; Ankle fusion: up to 10 cm^3

• Each fused joint can be rigidly stabilized with with at least 1 and no more than 3 screws across the fusion plane. (Supplemental pins and staples may be used, as well as supplemental screws and plates external to the fusion site(s))

• Willing and able to comply with all study requirements including all postoperative clinical and radiographic evaluations

• For women of childbearing potential (not post-menopausal for 12 months or surgically sterile), a urine pregnancy test with a negative result must be obtained at screening and within 24 hours prior to procedure. These trial participants must commit to adequate birth control (e.g., oral contraceptive, two methods of barrier birth control, or abstinence) through the 78 week follow-up

Exclusion Criteria:

• Bone deficit requiring a structural graft

• Charcot foot disease

• Radiographic evidence of open physes

• Prior arthroplasty, arthrodesis, major surgical repair or reconstruction of the index ankle or hindfoot joint(s)

• Requires osteotomy or fusion of the midfoot joints

• BMI greater than 45 kg/m^2

• Documented medical history of, or radiographic evidence of, a bone disease (e.g. avascular necrosis) or other condition (e.g., osteolysis) that would preclude the subject from receiving screw fixation in the opinion of the surgeon

• Requires intramedullary nail fixation or an external fixator

• Comorbidity that would limit the ability to administer any functional measurements such as FAAM-ADL

• Has at the time of surgery, a systemic infection or local infection at the site of surgery

• Medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the study or potentially decrease survival or interfere with ambulation or rehabilitation (e.g., history of transient ischemic attack, stroke or liver disease)

• HgbA1c level greater than or equal to 8%

• Known hypersensitivity to any of the components of the product [e.g. B2A peptide, Hydroxyapatite (HA): beta-tricalcium phosphate (βTCP), ceramic granule]

• Currently receiving treatment with a drug known to interfere with bone metabolism [e.g., systemic corticosteroid therapy (topical corticosteroid therapy is permissible), methotrexate]

• Has previously received treatment with a drug known to interfere with bone metabolism [e.g., systemic corticosteroid therapy (topical corticosteroid therapy is permissible), methotrexate] and in the opinion of the investigator could continue to negatively interfere with bone metabolism or bone healing

• History of any severe allergy or anaphylaxis, or a history of hypersensitivity to protein pharmaceuticals [e.g., monoclonal antibodies or gamma globulins, recombinant Bone Morphogenetic Proteins (BMPs)]

• Medical condition requiring radiation, chemotherapy or immunosuppression

• Have a prior or active history of malignancy (except for basal cell carcinoma of the skin)

• Has a history of autoimmune disease known to affect bone metabolism. Examples include spondyloarthropathies (e.g., ankylosing spondylitis, Crohn's disease, and ulcerative colitis), Juvenile Arthritis, Grave's disease and Hashimoto's thyroiditis; Rheumatoid Arthritis is allowed

• Have pathological or genetic liver disease or who have clinically significant, elevated baseline liver function enzymes

• Has obvious and/or documented alcohol or illicit drug addictions

• Is a prisoner in a correctional institution/facility

• Actively involved in litigation or workman's compensation

• Has participated in clinical studies evaluating investigational devices, pharmaceuticals or biologics within 6 months of randomization

• Requires chronic therapeutic use of NSAID during the first 6 post-operative weeks (except aspirin up to 325 mg bid for cardiovascular protection and/or DVT prophylaxis)

• Has previously been treated with, or exposed to, therapeutic levels of synthetic or recombinant BMPs

• Requires chronic subcutaneous or intravenous heparin therapies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Physician Research Group	Gilbert	Arizona	United States	85295
2	Arizona Research Center	Phoenix	Arizona	United States	85053
3	California Pacific Orthopaedics	San Francisco	California	United States	94118
4	University of Colorado School of Medicine	Aurora	Colorado	United States	80045
5	Hartford Hospital	Hartford	Connecticut	United States	06106
6	Andrews Orthopaedic and Sports Medicine Center	Gulf Breeze	Florida	United States	32561
7	Emory Orthopaedic and Spine Hospital	Atlanta	Georgia	United States	30329
8	Midwest Orthopedics at Rush	Chicago	Illinois	United States	60612
9	Loyola University Medical Center	Maywood	Illinois	United States	60153
10	Sinai Hospital of Baltimore, Inc / Rubin Institute for Advanced Orthopedics	Baltimore	Maryland	United States	21215
11	Medstar	Baltimore	Maryland	United States	21218
12	Orthopaedic Associates of Michigan, Research and Education Institute	Grand Rapids	Michigan	United States	49525
13	Michigan Orthopedic Center	Lansing	Michigan	United States	48910
14	TRIA Orthopaedic Center	Bloomington	Minnesota	United States	55431
15	Desert Orthopaedic Center	Las Vegas	Nevada	United States	89121
16	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
17	Rutgers	Newark	New Jersey	United States	07103
18	University of Rochester School of Medicine	Rochester	New York	United States	14642
19	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
20	OrthoCarolina Research Institute, Inc.	Charlotte	North Carolina	United States	28207
21	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19106
22	Reconstructive Orthopaedic Associates	Philadelphia	Pennsylvania	United States	19107
23	University Orthopedics Center	State College	Pennsylvania	United States	16801
24	Campbell Clinic Orthopaedics	Germantown	Tennessee	United States	38138
25	University of Texas Medical Branch	Galveston	Texas	United States	77555-0165
26	Baylor St. Luke's Medical Center	Houston	Texas	United States	77030
27	Texas Tech University Health Sciences Center	Lubbock	Texas	United States	79430
28	University of Virginia Health System	Charlottesville	Virginia	United States	22908
29	University of Alberta System	Edmonton	Alberta	Canada	T6G 2B7
30	Central Alberta Orthopedics	Red Deer	Alberta	Canada	T4N 6S4
31	St. Paul's Hospital	Vancouver	British Columbia	Canada	V6Z 1Y6
32	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 3A7
33	Ottawa Hospital Research Institute	Ottawa	Ontario	Canada	K1Y 4E9
34	St. Michael's Hospital	Toronto	Ontario	Canada	M5C 1R6
35	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
36	University of Laval	Quebec City	Quebec	Canada	G1V 4G2

Sponsors and Collaborators

• Ferring Pharmaceuticals

Investigators

• Study Director: Global Clinical Compliance, Ferring Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Mar 14, 2018
• Statistical Analysis Plan - Mar 27, 2017

More Information

Publications

None provided.

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03028415
• Other Study ID Numbers: 000226; G150153
• First Posted: Jan 23, 2017
• Last Update Posted: Mar 11, 2021
• Last Verified: Aug 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 19 sites (14 sites in the United States and 5 sites in Canada) between July 2017 to July 2020.
Pre-assignment Detail	A total of 80 subjects were screened in the trial, of which, 56 subjects were randomized. All the 56 randomized subjects were exposed to graft material: 39 subjects were exposed to AMPLEX and 17 subjects were exposed to autogenous bone graft (ABG).

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Period Title: Overall Study
STARTED	39	17
Modified Intention-to-treat (mITT) Population	39	17
COMPLETED	31	14
NOT COMPLETED	8	3

Baseline Characteristics

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)	Total
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant	Total of all reporting groups
Overall Participants	39	17	56
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.4 (12.0)	50.5 (14.4)	53.9 (12.8)
Age, Customized (participants) [Number]
<65 years	29 74.4%	14 82.4%	43 76.8%
>=65 years	10 25.6%	3 17.6%	13 23.2%
Sex: Female, Male (Count of Participants)
Female	18 46.2%	13 76.5%	31 55.4%
Male	21 53.8%	4 23.5%	25 44.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 5.9%	1 1.8%
Not Hispanic or Latino	39 100%	16 94.1%	55 98.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	2 11.8%	2 3.6%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	1 2.6%	0 0%	1 1.8%
Black or African American	2 5.1%	3 17.6%	5 8.9%
White	36 92.3%	12 70.6%	48 85.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	19 48.7%	10 58.8%	29 51.8%
Canada	20 51.3%	7 41.2%	27 48.2%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects Who Met All Five Criteria for Subject Performance Composite (SPC) Endpoint
Description	Proportion of subjects who met all the following criteria for the SPC endpoint at 52 weeks: 1. Improvement in pain on weight-bearing at fusion site (≥20 mm reduction from baseline on 100 mm visual analog scale [VAS]); 2. Absence of significant graft harvest site pain (<20 mm on 100 mm VAS); 3. Improvement in Foot and Ankle Ability Measure Activities of Daily Living subscale (FAAM-ADL) (≥8 points improvement from baseline); 4. Absence of device related or procedure related serious adverse events (up to week 52); 5. Absence of secondary surgical or nonsurgical interventions intended to promote fusion (up to week 52). The last observation carried forward was used for subjects with missing response status at 52 weeks.
Time Frame	At week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	39	17
Number [percentage of subjects]	79.5	35.3

2. Secondary Outcome

Title	Proportion of Subjects Achieving Computerized Tomography (CT) Radiographic Fusion Success
Description	Defined as ≥50% bone bridging across the joint space for the full complement of joints in the absence of secondary surgical or nonsurgical interventions intended to promote fusion. The last observation carried forward was used for subjects with missing response status at 52 weeks.
Time Frame	At week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	39	17
Number [percentage of subjects]	66.7	82.4

3. Secondary Outcome

Title	Proportion of Subjects Achieving CT Radiographic Fusion Success
Description	Defined as ≥50% bone bridging across the joint space for the full complement of joints in the absence of secondary surgical or nonsurgical interventions intended to promote fusion.
Time Frame	At week 12

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	38	17
Number [percentage of subjects]	47.4	58.8

4. Secondary Outcome

Title	Proportion of Subjects Achieving CT Radiographic Fusion Success
Description	Defined as ≥50% bone bridging across the joint space for the full complement of joints in the absence of secondary surgical or nonsurgical interventions intended to promote fusion.
Time Frame	At week 24

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	37	16
Number [percentage of subjects]	73.0	75.0

5. Secondary Outcome

Title	Proportion of Subjects With Change From Baseline in Pain on Weight-bearing at Fusion Site (>20 mm Reduction From Baseline on 100 mm VAS)
Description	Weight-bearing pain at the fusion site was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire. Subjects were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced, with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Improvement in pain on weight-bearing at the fusion site was defined as ≥ 20 mm reduction from baseline on 100 mm VAS, and is presented for this outcome measure.
Time Frame	Baseline, and at week 12

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	37	16
Number [percentage of subjects]	78.4	68.8

6. Secondary Outcome

Title	Proportion of Subjects With Change From Baseline in Pain on Weight-bearing at Fusion Site (>20 mm Reduction From Baseline on 100 mm VAS)
Description	Weight-bearing pain at the fusion site was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire. Subjects were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced, with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Improvement in pain on weight-bearing at the fusion site was defined as ≥ 20 mm reduction from baseline on 100 mm VAS, and is presented for this outcome measure.
Time Frame	Baseline, and at week 24

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	36	16
Number [percentage of subjects]	88.9	62.5

7. Secondary Outcome

Title	Proportion of Subjects With Change From Baseline in Pain on Weight-bearing at Fusion Site (>20 mm Reduction From Baseline on 100 mm VAS)
Description	Weight-bearing pain at the fusion site was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire. Subjects were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced, with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Improvement in pain on weight-bearing at the fusion site was defined as ≥ 20 mm reduction from baseline on 100 mm VAS, and is presented for this outcome measure.
Time Frame	Baseline, and at week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	32	15
Number [percentage of subjects]	90.6	80.0

8. Secondary Outcome

Title	Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS)
Description	Graft harvest site pain was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire, and was only assessed among subjects in the ABG group. Subjects in the ABG group were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Absence of significant graft harvest site pain was defined as <20 mm on 100 mm VAS, and is presented for this outcome measure.
Time Frame	At week 2

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	Autogenous Bone Graft (ABG)
Arm/Group Description	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	15
Number [percentage of subjects]	33.3

9. Secondary Outcome

Title	Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS)
Description	Graft harvest site pain was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire, and was only assessed among subjects in the ABG group. Subjects in the ABG group were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Absence of significant graft harvest site pain was defined as <20 mm on 100 mm VAS, and is presented for this outcome measure.
Time Frame	At week 6

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	Autogenous Bone Graft (ABG)
Arm/Group Description	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	15
Number [percentage of subjects]	60.0

10. Secondary Outcome

Title	Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS)
Description	Graft harvest site pain was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire, and was only assessed among subjects in the ABG group. Subjects in the ABG group were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Absence of significant graft harvest site pain was defined as <20 mm on 100 mm VAS, and is presented for this outcome measure.
Time Frame	At week 12

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	Autogenous Bone Graft (ABG)
Arm/Group Description	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	15
Number [percentage of subjects]	73.3

11. Secondary Outcome

Title	Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS)
Description	Graft harvest site pain was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire, and was only assessed among subjects in the ABG group. Subjects in the ABG group were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Absence of significant graft harvest site pain was defined as <20 mm on 100 mm VAS, and is presented for this outcome measure.
Time Frame	At week 24

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	Autogenous Bone Graft (ABG)
Arm/Group Description	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	15
Number [percentage of subjects]	60.0

12. Secondary Outcome

Title	Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS)
Description	Graft harvest site pain was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire, and was only assessed among subjects in the ABG group. Subjects in the ABG group were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Absence of significant graft harvest site pain was defined as <20 mm on 100 mm VAS, and is presented for this outcome measure.
Time Frame	At week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	Autogenous Bone Graft (ABG)
Arm/Group Description	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	16
Number [percentage of subjects]	68.8

13. Secondary Outcome

Title	Change From Baseline in FAAM-ADL
Description	Functional improvement was assessed using the Foot and Ankle Ability Measure Activities of Daily Living (FAAM-ADL) subscale, a subject self-assessment questionnaire that consists of 21 items pertaining to basic functional activities. Each item is scored on a 5 point Likert scale anchored by 4 (no difficulty at all) and 0 (unable to do). The total item subscale score ranges from 0 to 84, which are transformed to a scale of 0 to 100 as the final score. Higher scores represent a higher level of function, with 100 representing no dysfunction.
Time Frame	Baseline, and at week 12

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	37	16
Mean (Standard Deviation) [score on a scale]	11.16 (27.67)	7.17 (20.46)

14. Secondary Outcome

Title	Change From Baseline in FAAM-ADL
Description	Functional improvement was assessed using the e Foot and Ankle Ability Measure Activities of Daily Living (FAAM-ADL) subscale, a subject self-assessment questionnaire that consists of 21 items pertaining to basic functional activities. Each item is scored on a 5 point Likert scale anchored by 4 (no difficulty at all) and 0 (unable to do). The total item subscale score ranges from 0 to 84, which are transformed to a scale of 0 to 100 as the final score. Higher scores represent a higher level of function, with 100 representing no dysfunction.
Time Frame	Baseline, and at week 24

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	36	16
Mean (Standard Deviation) [score on a scale]	25.36 (23.82)	13.28 (17.30)

15. Secondary Outcome

Title	Change From Baseline in FAAM-ADL
Description	Functional improvement was assessed using the Foot and Ankle Ability Measure Activities of Daily Living (FAAM-ADL) subscale, a subject self-assessment questionnaire that consists of 21 items pertaining to basic functional activities. Each item is scored on a 5 point Likert scale anchored by 4 (no difficulty at all) and 0 (unable to do). The total item subscale score ranges from 0 to 84, which are transformed to a scale of 0 to 100 as the final score. Higher scores represent a higher level of function, with 100 representing no dysfunction.
Time Frame	Baseline, and at week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	32	15
Mean (Standard Deviation) [score on a scale]	34.99 (21.51)	11.37 (21.49)

16. Secondary Outcome

Title	Subject Performance Composite (SPC) Endpoint
Description	Proportion of subjects who met all the following criteria for the Subject Performance Composite (SPC) endpoint at 12 weeks: 1. Improvement in pain on weight-bearing at fusion site (≥20 mm reduction from baseline on 100 mm visual analog scale [VAS]); 2. Absence of significant graft harvest site pain (<20 mm on 100 mm VAS); 3. Improvement in Foot and Ankle Ability Measure Activities of Daily Living subscale (FAAM-ADL) (≥8 points improvement from baseline); 4. Absence of device related or procedure related serious adverse events (up to week 12); 5. Absence of secondary surgical or nonsurgical interventions intended to promote fusion (up to week 12).
Time Frame	At week 12

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	37	16
Number [percentage of subjects]	40.5	31.3

17. Secondary Outcome

Title	Subject Performance Composite (SPC) Endpoint
Description	Proportion of subjects who met all the following criteria for the SPC endpoint at 24 weeks: 1. Improvement in pain on weight-bearing at fusion site (≥20 mm reduction from baseline on 100 mm visual analog scale [VAS]); 2. Absence of significant graft harvest site pain (<20 mm on 100 mm VAS); 3. Improvement in Foot and Ankle Ability Measure Activities of Daily Living subscale (FAAM-ADL) (≥8 points improvement from baseline); 4. Absence of device related or procedure related serious adverse events (up to week 24); 5. Absence of secondary surgical or nonsurgical interventions intended to promote fusion (up to week 24).
Time Frame	At week 24

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	36	15
Number [percentage of subjects]	66.7	6.7

18. Secondary Outcome

Title	Change From Baseline in Short Form-12 (SF-12)
Description	The Short Form-12 (SF-12) Health Survey includes 12 questions from the SF-36 Health Survey. These include: 2 questions concerning physical functioning; 2 questions on role limitations because of physical health problems; 1 question on bodily pain; 1 question on general health perceptions; 1 question on vitality (energy/fatigue); 1 question on social functioning; 2 questions on role limitations because of emotional problems; and 2 questions on general mental health (psychological distress and psychological well-being). These eight domain scales were used to derive Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. All scores were calculated through scoring software. Domain scales and component summary scores ranged from 0 to 100, with a higher score considered better.
Time Frame	Baseline, and at week 24

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	36	16
SF-12 Physical component summary (Week 24)	9.1 (11.2)	5.3 (7.1)
SF-12 Mental component summary (Week 24)	2.0 (12.5)	-3.6 (9.2)

19. Secondary Outcome

Title	Change From Baseline in Short Form-12 (SF-12)
Description	The Short Form-12 (SF-12) Health Survey includes 12 questions from the SF-36 Health Survey. These include: 2 questions concerning physical functioning; 2 questions on role limitations because of physical health problems; 1 question on bodily pain; 1 question on general health perceptions; 1 question on vitality (energy/fatigue); 1 question on social functioning; 2 questions on role limitations because of emotional problems; and 2 questions on general mental health (psychological distress and psychological well-being). These eight domain scales were used to derive Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. All scores were calculated through scoring software. Domain scales and component summary scores ranged from 0 to 100, with a higher score considered better.
Time Frame	Baseline, and at week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set comprised all randomized subjects who had an attempted fusion of the index joint(s). Subjects were analyzed according to randomized (planned) treatment.

Arm/Group Title	AMPLEX	Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute	Autogenous Bone Graft (ABG): Control material administered by surgical implant
Measure Participants	32	15
SF-12 Physical component summary (Week 52)	10.5 (10.7)	3.8 (7.4)
SF-12 Mental component summary (Week 52)	4.4 (11.6)	-0.8 (11.0)

Adverse Events

Time Frame	From the signing of the informed consent up to 78 weeks
Adverse Event Reporting Description	A treatment-emergent AE was any AE occurring after the initiation of the surgery. If the timing of an AE could not be established in relation to the initiation of the surgery, it was considered as a treatment-emergent AE. Only treatment-emergent AEs are presented.
Arm/Group Title	AMPLEX		Autogenous Bone Graft (ABG)
Arm/Group Description	AMPLEX: A bone graft substitute		Autogenous Bone Graft (ABG): Control material administered by surgical implant
All Cause Mortality
	AMPLEX		Autogenous Bone Graft (ABG)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/17 (0%)
Serious Adverse Events
	AMPLEX		Autogenous Bone Graft (ABG)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/39 (17.9%)		7/17 (41.2%)
Eye disorders
Cataract	1/39 (2.6%)	1	0/17 (0%)	0
Glaucoma	0/39 (0%)	0	1/17 (5.9%)	1
Gastrointestinal disorders
Abdominal hernia	1/39 (2.6%)	1	0/17 (0%)	0
Colitis	0/39 (0%)	0	1/17 (5.9%)	1
General disorders
Impaired healing	0/39 (0%)	0	1/17 (5.9%)	1
Hepatobiliary disorders
Biliary colic	1/39 (2.6%)	1	0/17 (0%)	0
Cholecystitis	0/39 (0%)	0	1/17 (5.9%)	1
Infections and infestations
Candida infection	0/39 (0%)	0	1/17 (5.9%)	1
Pyelonephritis	1/39 (2.6%)	1	0/17 (0%)	0
Sepsis	0/39 (0%)	0	1/17 (5.9%)	1
Injury, poisoning and procedural complications
Overdose	1/39 (2.6%)	1	0/17 (0%)	0
Tibia fracture	0/39 (0%)	0	1/17 (5.9%)	1
Musculoskeletal and connective tissue disorders
Pseudarthrosis	1/39 (2.6%)	1	1/17 (5.9%)	1
Osteoarthritis	0/39 (0%)	0	1/17 (5.9%)	1
Renal and urinary disorders
Urinary retention	1/39 (2.6%)	1	0/17 (0%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/39 (0%)	0	1/17 (5.9%)	1
Vascular disorders
Peripheral arterial occlusive disease	0/39 (0%)	0	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	AMPLEX		Autogenous Bone Graft (ABG)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/39 (69.2%)		12/17 (70.6%)
Blood and lymphatic system disorders
Leukocytosis	1/39 (2.6%)	1	1/17 (5.9%)	1
Cardiac disorders
Tachycardia	0/39 (0%)	0	1/17 (5.9%)	1
Gastrointestinal disorders
Gastrooesophageal reflux disease	3/39 (7.7%)	3	1/17 (5.9%)	1
Nausea	3/39 (7.7%)	4	1/17 (5.9%)	1
Vomiting	2/39 (5.1%)	2	1/17 (5.9%)	1
Large intestine polyp	0/39 (0%)	0	2/17 (11.8%)	2
Abdominal pain	0/39 (0%)	0	1/17 (5.9%)	1
Haemorrhoids	0/39 (0%)	0	1/17 (5.9%)	1
General disorders
Oedema peripheral	3/39 (7.7%)	3	1/17 (5.9%)	1
Implant site irritation	1/39 (2.6%)	1	1/17 (5.9%)	1
Non-cardiac chest pain	1/39 (2.6%)	1	1/17 (5.9%)	1
Implant site pain	0/39 (0%)	0	1/17 (5.9%)	1
Peripheral swelling	0/39 (0%)	0	1/17 (5.9%)	1
Hepatobiliary disorders
Hepatic steatosis	0/39 (0%)	0	1/17 (5.9%)	1
Infections and infestations
Urinary tract infection	1/39 (2.6%)	3	2/17 (11.8%)	2
Acute sinusitis	0/39 (0%)	0	1/17 (5.9%)	1
Bronchitis	0/39 (0%)	0	1/17 (5.9%)	1
Gastroenteritis	0/39 (0%)	0	1/17 (5.9%)	1
Helicobacter infection	0/39 (0%)	0	1/17 (5.9%)	1
Herpes simplex	0/39 (0%)	0	1/17 (5.9%)	1
Upper respiratory tract infection	0/39 (0%)	0	1/17 (5.9%)	1
Injury, poisoning and procedural complications
Fall	2/39 (5.1%)	3	1/17 (5.9%)	1
Incision site hypoaesthesia	2/39 (5.1%)	2	1/17 (5.9%)	1
Incision site swelling	2/39 (5.1%)	2	0/17 (0%)	0
Limb injury	2/39 (5.1%)	2	0/17 (0%)	0
Procedural nausea	1/39 (2.6%)	1	1/17 (5.9%)	1
Wound dehiscence	2/39 (5.1%)	2	0/17 (0%)	0
Eschar	0/39 (0%)	0	1/17 (5.9%)	1
Procedural vomiting	0/39 (0%)	0	1/17 (5.9%)	1
Investigations
Gamma-glutamyltransferase increased	0/39 (0%)	0	1/17 (5.9%)	1
White blood cell count decreased	0/39 (0%)	0	1/17 (5.9%)	1
Metabolism and nutrition disorders
Hyperglycaemia	0/39 (0%)	0	1/17 (5.9%)	1
Hyperlipidaemia	0/39 (0%)	0	1/17 (5.9%)	1
Hypokalaemia	0/39 (0%)	0	1/17 (5.9%)	2
Hypomagnesaemia	0/39 (0%)	0	1/17 (5.9%)	2
Lactic acidosis	0/39 (0%)	0	1/17 (5.9%)	1
Type 2 diabetes mellitus	0/39 (0%)	0	1/17 (5.9%)	1
Vitamin B12 deficiency	0/39 (0%)	0	1/17 (5.9%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/39 (5.1%)	2	3/17 (17.6%)	3
Back pain	2/39 (5.1%)	2	2/17 (11.8%)	2
Pain in extremity	2/39 (5.1%)	2	2/17 (11.8%)	3
Plantar fasciitis	2/39 (5.1%)	2	1/17 (5.9%)	1
Osteoarthritis	2/39 (5.1%)	2	0/17 (0%)	0
Tendonitis	1/39 (2.6%)	1	1/17 (5.9%)	1
Joint swelling	0/39 (0%)	0	1/17 (5.9%)	1
Muscle spasms	0/39 (0%)	0	1/17 (5.9%)	1
Nervous system disorders
Hypoaesthesia	3/39 (7.7%)	3	0/17 (0%)	0
Headache	1/39 (2.6%)	1	1/17 (5.9%)	1
Lumbar radiculopathy	0/39 (0%)	0	1/17 (5.9%)	1
Seizure	0/39 (0%)	0	1/17 (5.9%)	1
Syncope	0/39 (0%)	0	1/17 (5.9%)	1
Psychiatric disorders
Insomnia	1/39 (2.6%)	1	1/17 (5.9%)	1
Anxiety	0/39 (0%)	0	1/17 (5.9%)	1
Renal and urinary disorders
Acute kidney injury	0/39 (0%)	0	1/17 (5.9%)	1
Respiratory, thoracic and mediastinal disorders
Bronchospasm	0/39 (0%)	0	1/17 (5.9%)	1
Skin and subcutaneous tissue disorders
Skin ulcer	1/39 (2.6%)	1	1/17 (5.9%)	2
Ingrowing nail	0/39 (0%)	0	1/17 (5.9%)	1
Vascular disorders
Hypertension	1/39 (2.6%)	1	2/17 (11.8%)	2

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 the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.