Bioequivalence Study of Denosumab CP4 Drug Product and Commercially Available Denosumab CP2 Drug Product

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02053753
• Collaborator: (none)
• Enrollment: 146
• Locations: 2
• Arms: 2
• Duration (Months): 5.9
• Patients Per Site: 73
• Patients Per Site Per Month: 12.3

Study Details

Study Description

Brief Summary

To evaluate the bioequivalence based on pharmacokinetics (PK) of a single 120 mg subcutaneous dose of denosumab administered to healthy volunteers using denosumab CP4 or denosumab CP2 drug products.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteer	Drug: Denosumab CP4; Drug: Denosumab CP2	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 146 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Randomized, Single-Dose, Parallel-Group Study in Healthy Volunteers to Assess the Bioequivalence of a 120 mg Denosumab Subcutaneous Dose When Administered as Denosumab CP4 Drug Product or as Commercially Available Denosumab CP2 Drug Product
• Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Drug Product CP4 Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.	Drug: Denosumab CP4; Denosumab produced by a process referred to as CP4, administered subcutaneously.
Experimental: Drug Product CP2 Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.	Drug: Denosumab CP2; Denosumab produced by a process referred to as CP2, administered subcutaneously.; Other Names: XGEVA®

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Drug Concentration (Cmax) of Denosumab [Day 1 predose up to day 127]

   Serum denosumab concentration-time data were analyzed by non-compartmental methods. Serum concentrations below the LLOQ (20.0 ng/mL) were set to 0 before data analysis.

2. Area Under the Drug Concentration-time Curve From Time 0 to 18 Weeks Post-dose (AUC0-18 Weeks) of Denosumab [Day 1 predose up to day 127]

   Serum denosumab concentration-time data were analyzed by non-compartmental methods. Serum concentrations below the LLOQ (20.0 ng/mL) were set to 0 before data analysis.

Secondary Outcome Measures

1. Time to Maximum Observed Concentration (Tmax) of Denosumab [Day 1 predose up to day 127]

   Serum denosumab concentration-time data were analyzed by non-compartmental methods. Serum concentrations below the LLOQ (20.0 ng/mL) were set to 0 before data analysis.

2. Half-life (T1/2) of Denosumab [Day 1 predose up to day 127]

   Serum denosumab concentration-time data were analyzed by non-compartmental methods. Serum concentrations below the LLOQ (20.0 ng/mL) were set to 0 before data analysis.

3. Area Under the Serum C-telopeptide (CTX1) Percent Inhibition-Time Curve From Time 0 to 18 Weeks Post-dose (AUEC0-18 Weeks) [Day 1 predose up to day 127]

   Serum CTX1 concentration-time data were analyzed by non-compartmental methods. Serum CTX1 concentrations below the LLOQ (0.0490 ng/mL) were set to 0.0490 ng/mL before data analysis. AUEC0-18 weeks was estimated using the linear-log trapezoidal method.

4. Maximum Percent Inhibition (Imax) of Serum CTX1 [Day 1 predose up to day 127]

   Serum CTX1 concentration-time data were analyzed by non-compartmental methods. Serum CTX1 concentrations below the LLOQ (0.0490 ng/mL) were set to 0.0490 ng/mL before data analysis.

5. Time to Reach Maximum Percent Inhibition (Tmax) of Serum CTX1 [Day 1 predose up to day 127]

   Serum CTX1 concentration-time data were analyzed by non-compartmental methods. Serum CTX1 concentrations below the LLOQ (0.0490 ng/mL) were set to 0.0490 ng/mL before data analysis.

6. Number of Participants With Adverse Events [From the first dose of denosumab through day 126]

   A treatment-related adverse event (TRAE) is any treatment-emergent adverse event (AE) that per investigator review has a reasonable possibility of being caused by the investigational product.

7. Number of Participants Who Developed Anti-denosumab Antibodies [Predose on day 1, and days 29, 67 and 127]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Key Inclusion:

• Healthy male and female, ages ≥ 18 to ≤ 65 years (inclusive)

• Body weight > 60 to < 100 kg at time of screening

• Clinically acceptable physical exams and laboratory tests (blood hematology, blood chemistry, urinalysis) and no history or evidence of any clinically significant medical disorder that would pose a risk to subject safety or interfere with study evaluations or procedures

• Normal or clinically acceptable electrocardiogram (ECG) (12-lead reporting heart rate and PR, QRS, QT, and QTc intervals) at screening

• Willing to be confined to the research facility for 2 consecutive nights

• Subject will be available for follow-up assessments

Exclusion Criteria:

Prior diagnosis of bone disease, or any condition that will affect bone metabolism such as, but not limited to: osteoporosis, osteogenesis imperfecta, hyperparathyroidism, hyperthyroidism, hypothyroidism, osteomalacia, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, current flare-up of osteoarthritis and/or gout, active malignancy, renal disease (defined as glomerular filtration rate [GFR] < 45 mL/min), Paget's disease of the bone, recent bone fracture (within 6 months), malabsorption syndrome

• Presents with any psychiatric disorder, which may prevent the subject from completing the study or interfere with the interpretation of the study results

• Significant changes in physical activity during the 6 months before study drug administration or constant levels of intense physical exercise

• Prior use of any non-Amgen approved medications within 4 weeks or 5-half lives (whichever time period is longer) of study drug administration and for the duration of the study. This includes medications such as, but not limited to: bisphosphonates, fluoride, hormone replacement therapy (ie, estrogen) or selective estrogen receptor modulator, such as ralaxofene, calcitonin, strontium, parathyroid hormone or derivatives, supplemental vitamin D [>1000 IU/day], glucocorticosteroids, anabolic steroids, calcitriol, diuretics, over the counter medications, herbal supplements

• Positive for human immunodeficiency virus (HIV) at screening or known diagnosis of acquired immune deficiency syndrome (AIDS)

• Positive hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B) or detectable hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR) at screening (indicative of active hepatitis C - screening is generally done by hepatitis C antibody [HepCAb], followed by hepatitis C virus RNA by PCR if HepCAb is positive)

• Known sensitivity to any of the products to be administered during the study

• Prior denosumab administration

• Receiving or has received any investigational drug (or is currently using an investigational device) within 30 days before receiving study drug, or at least 10 times the respective elimination half-life (whichever period is longer) and for the duration of the study

• Women with a positive pregnancy test at screening or day-1

• Men and women of reproductive potential who are unwilling to practice a highly effective method of birth control while on study through 5 months after receiving the last dose of study drug. Highly effective methods of birth control include sexual abstinence (men, women); vasectomy; or a condom with spermicide (men) in combination with either barrier methods, hormonal birth control or intrauterine device (women)

• Women who are lactating/breastfeeding or who plan to breastfeed while on study through 5 half-lives after receiving the dose of study drug

• Women planning to become pregnant while on study through 5 months after receiving the dose of study drug

• Men with partners who are pregnant or planning to become pregnant while the subject is on study through 5 months after receiving the last dose of study drug

• Unwilling or unable to limit alcohol consumption throughout the course of the study. Alcohol is prohibited 24 hours prior to screening, 24 hours prior to check-in on day -1, and throughout confinement. Alcohol is also limited to no more than 2 drinks per day during the outpatient period of the study through completion of day 127 (EOS). A standard drink is equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt liquor, 5 ounces of wine, or 1.5 ounces of 80 proof distilled spirits

• Positive urine screen for alcohol and/or drugs with a high potential for abuse at screening or day -1. Rescreening of the subject within 48 hours of a positive result is permitted

• Any other condition that might reduce the chance of obtaining data required by protocol or that might compromise the ability to give truly informed consent and/or comply with study procedures

• Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (eg, tooth extraction, dental implants, oral surgery in the past 6 months), poor oral hygiene, periodontal, and/or pre-existing dental disease

• Recent tooth extraction (within 6 months of screening visit)

• Evidence of hypocalcemia at screening

• Known vitamin D deficiency

• Known intolerance to calcium or vitamin D supplements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Cypress	California	United States	90630
2	Research Site	San Antonio	Texas	United States	78209

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02053753
• Other Study ID Numbers: 20120186
• First Posted: Feb 4, 2014
• Last Update Posted: Dec 29, 2017
• Last Verified: Jul 1, 2017

• Keywords provided by Amgen: denosumab, bioequivalence
• Additional relevant MeSH terms: Denosumab

Study Results

Participant Flow

Recruitment Details	This study was conducted at 2 centers in the United States.
Pre-assignment Detail	Participants were randomized in a 1:1 ratio to receive a single 120-mg dose of denosumab either as a 1.7 mL single injection of 70 mg/mL denosumab produced using the new CP4 process or as a 1.7 mL single injection of 70 mg/mL denosumab produced from the current CP2 process.

Arm/Group Title	Denosumab CP4	Denosumab CP2
Arm/Group Description	Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.	Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.
Period Title: Overall Study
STARTED	72	74
Received Treatment	71	71
COMPLETED	65	66
NOT COMPLETED	7	8

Baseline Characteristics

Arm/Group Title	Denosumab CP4	Denosumab CP2	Total
Arm/Group Description	Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.	Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.	Total of all reporting groups
Overall Participants	71	71	142
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.9 (10.9)	37.6 (11.3)	38.3 (11.1)
Sex: Female, Male (Count of Participants)
Female	29 40.8%	33 46.5%	62 43.7%
Male	42 59.2%	38 53.5%	80 56.3%
Race/Ethnicity, Customized (participants) [Number]
Asian	5 7%	4 5.6%	9 6.3%
Black (or African American)	24 33.8%	24 33.8%	48 33.8%
Multiple	3 4.2%	1 1.4%	4 2.8%
White	39 54.9%	42 59.2%	81 57%
Race/Ethnicity, Customized (participants) [Number]
Hispanic/Latino	20 28.2%	23 32.4%	43 30.3%
Not Hispanic/Latino	51 71.8%	48 67.6%	99 69.7%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Drug Concentration (Cmax) of Denosumab
Description	Serum denosumab concentration-time data were analyzed by non-compartmental methods. Serum concentrations below the LLOQ (20.0 ng/mL) were set to 0 before data analysis.
Time Frame	Day 1 predose up to day 127

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) concentration analysis set includes all participants who received denosumab and had at least one PK sample collected. Two participants were excluded from all PK analyses because insufficient samples were available (≥ 3 missing consecutive samples) for calculation of PK variables.

Arm/Group Title	Denosumab CP4	Denosumab CP2
Arm/Group Description	Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.	Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.
Measure Participants	71	69
Mean (Standard Deviation) [μg/mL]	12.7 (3.53)	11.8 (3.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab CP4, Denosumab CP2
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The 2 treatments were considered bioequivalent if the 90% CIs for the ratio of the geometric means were between 0.80 and 1.25.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometrc Means (CP4:CP2)
	Estimated Value	1.084
	Confidence Interval	(2-Sided) 90%; 0.995 to 1.181
	Parameter Dispersion	Type: Value:
	Estimation Comments	The ratio and confidence interval of the geometric means are based on natural log scale data converted back to the original scale.

2. Primary Outcome

Title	Area Under the Drug Concentration-time Curve From Time 0 to 18 Weeks Post-dose (AUC0-18 Weeks) of Denosumab
Description	Serum denosumab concentration-time data were analyzed by non-compartmental methods. Serum concentrations below the LLOQ (20.0 ng/mL) were set to 0 before data analysis.
Time Frame	Day 1 predose up to day 127

Outcome Measure Data

Analysis Population Description

The PK concentration analysis set; 2 participants were excluded from all PK analyses because insufficient samples were available for calculation of PK variables and a further 11 participants were excluded from the analysis of AUC0-18 weeks because all samples after week 16 were missing.

Arm/Group Title	Denosumab CP4	Denosumab CP2
Arm/Group Description	Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.	Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.
Measure Participants	64	65
Mean (Standard Deviation) [day*μg/mL]	579 (190)	555 (166)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab CP4, Denosumab CP2
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The 2 treatments were considered bioequivalent if the 90% CIs for the ratio of the geometric means were between 0.80 and 1.25.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Means (CP4:CP2)
	Estimated Value	1.028
	Confidence Interval	(2-Sided) 90%; 0.934 to 1.131
	Parameter Dispersion	Type: Value:
	Estimation Comments	The ratio and confidence interval of the geometric means are based on natural log scale data converted back to the original scale.

3. Secondary Outcome

Title	Time to Maximum Observed Concentration (Tmax) of Denosumab
Description	Serum denosumab concentration-time data were analyzed by non-compartmental methods. Serum concentrations below the LLOQ (20.0 ng/mL) were set to 0 before data analysis.
Time Frame	Day 1 predose up to day 127

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) concentration analysis set includes all participants who received denosumab and had at least one PK sample collected. Two participants were excluded from all PK analyses because insufficient samples were available (≥ 3 missing consecutive samples) for calculation of PK variables.

Arm/Group Title	Denosumab CP4	Denosumab CP2
Arm/Group Description	Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.	Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.
Measure Participants	71	69
Median (Full Range) [days]	6.9	7.0

4. Secondary Outcome

Title	Half-life (T1/2) of Denosumab
Description	Serum denosumab concentration-time data were analyzed by non-compartmental methods. Serum concentrations below the LLOQ (20.0 ng/mL) were set to 0 before data analysis.
Time Frame	Day 1 predose up to day 127

Outcome Measure Data

Analysis Population Description

The PK concentration analysis set; 2 participants were excluded from all PK analyses because insufficient samples were available for calculation of PK variables and a further 11 participants were excluded from the analysis of T1/2 because all samples after week 16 were missing.

Arm/Group Title	Denosumab CP4	Denosumab CP2
Arm/Group Description	Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.	Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.
Measure Participants	64	65
Mean (Standard Deviation) [days]	23.9 (10.1)	22.4 (10.2)

5. Secondary Outcome

Title	Area Under the Serum C-telopeptide (CTX1) Percent Inhibition-Time Curve From Time 0 to 18 Weeks Post-dose (AUEC0-18 Weeks)
Description	Serum CTX1 concentration-time data were analyzed by non-compartmental methods. Serum CTX1 concentrations below the LLOQ (0.0490 ng/mL) were set to 0.0490 ng/mL before data analysis. AUEC0-18 weeks was estimated using the linear-log trapezoidal method.
Time Frame	Day 1 predose up to day 127

Outcome Measure Data

Analysis Population Description

The pharmacodynamic (PD) analysis set includes all participants who received denosumab and had at least one sCTX1 sample collected. Eleven participants were excluded from the analysis of AUEC0-18 weeks because no samples after week 16 were collected.

Arm/Group Title	Denosumab CP4	Denosumab CP2
Arm/Group Description	Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.	Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.
Measure Participants	65	66
Mean (Standard Deviation) [day*percent inhibition]	8380 (2050)	8190 (2250)

6. Secondary Outcome

Title	Maximum Percent Inhibition (Imax) of Serum CTX1
Description	Serum CTX1 concentration-time data were analyzed by non-compartmental methods. Serum CTX1 concentrations below the LLOQ (0.0490 ng/mL) were set to 0.0490 ng/mL before data analysis.
Time Frame	Day 1 predose up to day 127

Outcome Measure Data

Analysis Population Description

The pharmacodynamic analysis set includes all participants who received denosumab and had at least one sCTX1 sample collected.

Arm/Group Title	Denosumab CP4	Denosumab CP2
Arm/Group Description	Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.	Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.
Measure Participants	71	71
Mean (Standard Deviation) [percent inhibition]	69.8 (17.0)	70.3 (13.7)

7. Secondary Outcome

Title	Time to Reach Maximum Percent Inhibition (Tmax) of Serum CTX1
Description	Serum CTX1 concentration-time data were analyzed by non-compartmental methods. Serum CTX1 concentrations below the LLOQ (0.0490 ng/mL) were set to 0.0490 ng/mL before data analysis.
Time Frame	Day 1 predose up to day 127

Outcome Measure Data

Analysis Population Description

The pharmacodynamic analysis set includes all participants who received denosumab and had at least one sCTX1 sample collected.

Arm/Group Title	Denosumab CP4	Denosumab CP2
Arm/Group Description	Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.	Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.
Measure Participants	71	71
Median (Full Range) [days]	3.01	3.96

8. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	A treatment-related adverse event (TRAE) is any treatment-emergent adverse event (AE) that per investigator review has a reasonable possibility of being caused by the investigational product.
Time Frame	From the first dose of denosumab through day 126

Outcome Measure Data

Analysis Population Description

All participants who received denosumab

Arm/Group Title	Denosumab CP4	Denosumab CP2
Arm/Group Description	Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.	Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.
Measure Participants	71	71
Any adverse event	26 36.6%	24 33.8%
Serious adverse events	0 0%	1 1.4%
AEs leading to discontinuation of denosumab	0 0%	0 0%
Fatal adverse events	0 0%	0 0%
Treatment-related adverse events (TRAEs)	4 5.6%	6 8.5%
Treatment-related serious adverse events	0 0%	0 0%
TRAEs leading to discontinuation of denosumab	0 0%	0 0%
Treatment-related fatal adverse events	0 0%	0 0%

9. Secondary Outcome

Title	Number of Participants Who Developed Anti-denosumab Antibodies
Time Frame	Predose on day 1, and days 29, 67 and 127

Outcome Measure Data

Analysis Population Description

All participants who received denosumab

Arm/Group Title	Denosumab CP4	Denosumab CP2
Arm/Group Description	Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.	Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.
Measure Participants	71	71
Number [participants]	0 0%	0 0%

Adverse Events

Time Frame	From the first dose of denosumab through day 126
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Denosumab CP4		Denosumab CP2
Arm/Group Description	Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.		Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.
All Cause Mortality
	Denosumab CP4		Denosumab CP2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Denosumab CP4		Denosumab CP2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/71 (0%)		1/71 (1.4%)
Infections and infestations
Abscess limb	0/71 (0%)		1/71 (1.4%)
Other (Not Including Serious) Adverse Events
	Denosumab CP4		Denosumab CP2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/71 (36.6%)		24/71 (33.8%)
Endocrine disorders
Goitre	0/71 (0%)		1/71 (1.4%)
Eye disorders
Eye pruritus	1/71 (1.4%)		0/71 (0%)
Scleral discolouration	1/71 (1.4%)		0/71 (0%)
Gastrointestinal disorders
Abdominal pain	1/71 (1.4%)		0/71 (0%)
Aphthous stomatitis	1/71 (1.4%)		0/71 (0%)
Constipation	0/71 (0%)		1/71 (1.4%)
Diarrhoea	1/71 (1.4%)		1/71 (1.4%)
Dry mouth	1/71 (1.4%)		0/71 (0%)
Dyspepsia	0/71 (0%)		1/71 (1.4%)
Food poisoning	0/71 (0%)		1/71 (1.4%)
Gastric mucosa erythema	1/71 (1.4%)		0/71 (0%)
Inguinal hernia	1/71 (1.4%)		0/71 (0%)
Nausea	3/71 (4.2%)		0/71 (0%)
Tooth loss	1/71 (1.4%)		0/71 (0%)
Vomiting	1/71 (1.4%)		0/71 (0%)
General disorders
Asthenia	1/71 (1.4%)		0/71 (0%)
Chills	1/71 (1.4%)		0/71 (0%)
Injection site reaction	0/71 (0%)		1/71 (1.4%)
Malaise	0/71 (0%)		1/71 (1.4%)
Vessel puncture site haematoma	1/71 (1.4%)		0/71 (0%)
Vessel puncture site pain	0/71 (0%)		1/71 (1.4%)
Infections and infestations
Conjunctivitis viral	1/71 (1.4%)		0/71 (0%)
Nasopharyngitis	0/71 (0%)		1/71 (1.4%)
Pilonidal cyst	0/71 (0%)		1/71 (1.4%)
Pulpitis dental	0/71 (0%)		1/71 (1.4%)
Tooth infection	0/71 (0%)		1/71 (1.4%)
Upper respiratory tract infection	2/71 (2.8%)		2/71 (2.8%)
Viral infection	0/71 (0%)		1/71 (1.4%)
Injury, poisoning and procedural complications
Arthropod bite	0/71 (0%)		1/71 (1.4%)
Excoriation	0/71 (0%)		2/71 (2.8%)
Fall	0/71 (0%)		1/71 (1.4%)
Joint injury	0/71 (0%)		1/71 (1.4%)
Ligament sprain	0/71 (0%)		1/71 (1.4%)
Tongue injury	0/71 (0%)		1/71 (1.4%)
Tooth fracture	1/71 (1.4%)		0/71 (0%)
Investigations
Blood calcium decreased	2/71 (2.8%)		2/71 (2.8%)
Blood phosphorus decreased	1/71 (1.4%)		2/71 (2.8%)
Metabolism and nutrition disorders
Hypercalcaemia	1/71 (1.4%)		0/71 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/71 (1.4%)		2/71 (2.8%)
Exostosis	1/71 (1.4%)		0/71 (0%)
Muscle disorder	0/71 (0%)		1/71 (1.4%)
Musculoskeletal discomfort	1/71 (1.4%)		0/71 (0%)
Musculoskeletal pain	1/71 (1.4%)		1/71 (1.4%)
Myalgia	1/71 (1.4%)		0/71 (0%)
Neck pain	1/71 (1.4%)		0/71 (0%)
Pain in extremity	1/71 (1.4%)		0/71 (0%)
Plantar fasciitis	1/71 (1.4%)		0/71 (0%)
Nervous system disorders
Dizziness	0/71 (0%)		1/71 (1.4%)
Headache	6/71 (8.5%)		4/71 (5.6%)
Renal and urinary disorders
Haematuria	0/71 (0%)		1/71 (1.4%)
Reproductive system and breast disorders
Haematospermia	0/71 (0%)		1/71 (1.4%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	1/71 (1.4%)		0/71 (0%)
Rhinorrhoea	1/71 (1.4%)		0/71 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/71 (0%)		1/71 (1.4%)
Urticaria	0/71 (0%)		1/71 (1.4%)
Vascular disorders
Phlebitis	0/71 (0%)		1/71 (1.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.