Evaluation of Radiesse® Dermal Filler for Hand Rejuvenation

To evaluate the efficacy of Radiesse for hand treatment as measured by a ≥ 1-point change on the 5-point Busso Hand Volume Severity Scale (BHVSS) between baseline and 3 months, by hand, among treated subjects and untreated controls. A measure of successful or improved treatment effect is demonstrated by a decrease in BHVSS score. Busso Hand Volume Severity Scale (BHVSS) rating definitions are as follows: 4 = All 3 central tendons are fully exposed when hand is at rest; 3 = All 3 central tendons are partially exposed with 1 to 2 tendons fully exposed when hand is at rest; 2 = All 3 central tendons are partially exposed when hand is at rest; 1 = One or 2 central tendons are slightly exposed when hand is at rest; and 0 = No tendons exposed when hand is at rest.

Time frame: 3 months from baseline

Population: 3-month BHVSS: safety analysis set, which is the subset of subjects who have been exposed to the study medication at least once

To evaluate the efficacy of Radiesse for hand treatment as measured by a ≥ 1-point change on the 5-point Busso Hand Volume Severity Scale (BHVSS) between baseline and 3 months, by subject, among treated subjects and untreated controls. A measure of successful or improved treatment effect is demonstrated by a decrease in BHVSS score. Busso Hand Volume Severity Scale (BHVSS) rating definitions are as follows: 4 = All 3 central tendons are fully exposed when hand is at rest; 3 = All 3 central tendons are partially exposed with 1 to 2 tendons fully exposed when hand is at rest; 2 = All 3 central tendons are partially exposed when hand is at rest; 1 = One or 2 central tendons are slightly exposed when hand is at rest; and 0 = No tendons exposed when hand is at rest.

Time frame: 3 months from baseline

To evaluate the efficacy of Radiesse for hand treatment as measured by mean change on the 5-point Busso Hand Volume Severity Scale (BHVSS) between baseline and 3 months, by hand, among treated subjects and untreated controls. Ratings were completed by three, blinded evaluators. A measure of successful or improved treatment effect is demonstrated by a decrease in BHVSS score. Busso Hand Volume Severity Scale (BHVSS) rating definitions are as follows: 4 = All 3 central tendons are fully exposed when hand is at rest; 3 = All 3 central tendons are partially exposed with 1 to 2 tendons fully exposed when hand is at rest; 2 = All 3 central tendons are partially exposed when hand is at rest; 1 = One or 2 central tendons are slightly exposed when hand is at rest; and 0 = No tendons exposed when hand is at rest.

Time frame: 3 months from baseline

Population: 3-month BHVSS: safety analysis set, which is the subset of subjects who have been exposed to the study medication at least once. 2 subjects were enrolled \& withdrew prior to treatment.

To evaluate the efficacy of Radiesse for hand treatment as measured by ≥ 1-point change on the 5-point Busso Hand Volume Severity Scale (BHVSS) between baseline and 3, 6, 9 and 12 months, by hand, among treated subjects. A measure of successful or improved treatment effect is demonstrated by a decrease in BHVSS score. Busso Hand Volume Severity Scale (BHVSS) rating definitions are as follows: 4 = All 3 central tendons are fully exposed when hand is at rest; 3 = All 3 central tendons are partially exposed with 1 to 2 tendons fully exposed when hand is at rest; 2 = All 3 central tendons are partially exposed when hand is at rest; 1 = One or 2 central tendons are slightly exposed when hand is at rest; and 0 = No tendons exposed when hand is at rest.

Time frame: 3, 6, 9, and 12 months from baseline

Population: BHVSS: safety analysis set, or subset of subjects exposed to study medication at least once. After 3 months, untreated controls were treated with Radiesse. All subjects (n=98) were followed to 9-months post-treatment; only the original treatment group (n=75) was followed to 12-months post-treatment.

To evaluate the efficacy of Radiesse for hand treatment as measured by ≥ 1-point change on the 5-point Busso Hand Volume Severity Scale (BHVSS) between baseline and 3, 6, 9 and 12 months, by subject, among treated subjects. A measure of successful or improved treatment effect is demonstrated by a decrease in BHVSS score. Busso Hand Volume Severity Scale (BHVSS) rating definitions are as follows: 4 = All 3 central tendons are fully exposed when hand is at rest; 3 = All 3 central tendons are partially exposed with 1 to 2 tendons fully exposed when hand is at rest; 2 = All 3 central tendons are partially exposed when hand is at rest; 1 = One or 2 central tendons are slightly exposed when hand is at rest; and 0 = No tendons exposed when hand is at rest.

Time frame: 3, 6, 9, and 12 months from baseline

Population: 3-,6-, 9-, and 12-month BHVSS: safety analysis set, which is the subset of subjects who have been exposed to the study medication at least once. After 3 months, the untreated controls were treated with Radiesse and were followed as per the original treatment group.

Effectiveness was measured by evaluating subject's difficulty in performing routine activities during the prior week according to a 5-point Michigan Hand Outcomes Questionnaire (MHOQ) scale at baseline and 3, 6, 9, and 12 months post-baseline, by hand. Activities were as follows and were graded by subject as 1 = not at all difficult, 2 = a little difficult, 3 = somewhat difficult, 4 = moderately difficult, and 5 = very difficult: 1. Turn a knob 2. Pick up a coin 3. Hold a glass of water 4. Turn a key in a lock 5. Hold a frying pan

Time frame: Baseline and 3, 6, 9, and 12 months post-treatment

Population: Safety analysis set; see previously reported population description. 1 subject did not complete baseline, right hand questionnaire. 2 subjects did not complete baseline, left hand questionnaire.1 subject did not complete 6-month questionnaire for either hand.

Effectiveness was measured by evaluating subject's difficulty in performing routine activities, that require both hands, during the prior week according to a 5-point Michigan Hand Outcomes Questionnaire (MHOQ) scale at baseline and 3, 6, 9, and 12 months post-baseline. Activities were as follows and were graded by subject as 1 = not at all difficult, 2 = a little difficult, 3 = somewhat difficult, 4 = moderately difficult, and 5 = very difficult: 1. Open a jar 2. Button a shirt / blouse 3. Eat with a knife and fork 4. Carry a grocery bag 5. Wash dishes 6. Wash your hair 7. Tie shoelaces / knots

Time frame: Baseline and 3, 6, 9, and 12 months post-treatment

Population: Safety analysis set; see previously reported population description. 1 subject did not complete baseline questionnaire; 1 subject did not complete 6-month questionnaire.

To evaluate the efficacy of Radiesse Injectable Dermal Filler for hand treatment as measured by a Global Aesthetic Improvement Scale (GAIS), by hand, as completed by three, blinded evaluators.

Time frame: 3 months from baseline

Population: 3-month GAIS: safety analysis set, which is the subset of subjects who have been exposed to the study medication at least once. 2 subjects were enrolled \& withdrew prior to treatment.

To evaluate the efficacy of Radiesse for hand treatment as measured by Global Aesthetic Improvement Scale (GAIS) between baseline and 3, 6, 9, and 12 months, by hand, among all treated subjects. Ratings were completed by three, blinded evaluators.

Time frame: 3, 6, 9, and 12 months from baseline

Population: GAIS: safety analysis set, or subset of subjects exposed to study medication at least once. After 3 months, untreated controls were treated with Radiesse. All subjects (n=98) were followed to 9-months post-treatment; only the original treatment group (n=75) was followed to 12-months post-treatment.

Effectiveness was measured by evaluating changes in hand appearance, by subject, using the GAIS completed by three, blinded evaluators

Time frame: 3 months from baseline

Population: 3-month BHVSS: safety analysis set, which is the subset of subjects who have been exposed to the study medication at least once

Effectiveness was measured by evaluating changes in hand appearance, by subject, between baseline and 3, 6, 9 and 12 months, by subject, among treated subjects using the GAIS completed by three, blinded evaluators

Time frame: 3, 6, 9, and 12 months from baseline

Population: GAIS: safety analysis set, or subset of subjects exposed to study medication at least once. After 3 months, untreated controls were treated with Radiesse. All subjects (n=98) were followed to 9-months post-treatment; only the original treatment group (n=75) was followed to 12-months post-treatment.

To evaluate the efficacy of Radiesse for hand treatment as measured by mean change on the 5-point Busso Hand Volume Severity Scale (BHVSS) between baseline and 3, 6, 9, and 12 months, by hand, among all treated subjects. Ratings were completed by three, blinded evaluators. A measure of successful or improved treatment effect is demonstrated by a decrease in BHVSS score. Busso Hand Volume Severity Scale (BHVSS) rating definitions are as follows: 4 = All 3 central tendons are fully exposed when hand is at rest; 3 = All 3 central tendons are partially exposed with 1 to 2 tendons fully exposed when hand is at rest; 2 = All 3 central tendons are partially exposed when hand is at rest; 1 = One or 2 central tendons are slightly exposed when hand is at rest; and 0 = No tendons exposed when hand is at rest.

Time frame: 3, 6, 9, and 12 months from baseline

Population: BHVSS: safety analysis set or subset of subjects exposed to study medication at least once. After 3 months, untreated controls were treated with Radiesse. All subjects (n=98) followed to 9-months post-treatment; only the original treatment group (n=75) was followed to 12-months post-treatment. 2 subjects were enrolled \& withdrew prior to treatment.

Effectiveness was measured by evaluating subject's hand function during the prior week according to a 5-point Michigan Hand Outcomes Questionnaire (MHOQ) scale at baseline and 3, 6, 9, and 12 months post-baseline, by hand. Questions were as follows and were graded by subject as 1 = very good, 2 = good, 3 = fair, 4 = poor, and 5 = very poor: 1. Overall, how well did you hand work? 2. How well did your fingers move? 3. How well did your wrist move? 4. How was the strength in your hand? 5. How was the sensation (feeling) in your hand?

Time frame: Baseline and 3, 6, 9, and 12 months post-treatment

Population: Safety analysis set, or subset of subjects exposed to study medication at least once. After 3 months, untreated controls were treated with Radiesse. All subjects (n=98) were followed to 9-months post-treatment; only the original treatment group (n=75) was followed to 12-months post-treatment. 1 subject did not complete questionnaire at 6 months.

Effectiveness was measured by evaluating subject's ability to work normally, during the prior week according to a 5-point Michigan Hand Outcomes Questionnaire (MHOQ) scale at baseline and 3, 6, 9, and 12 months post-baseline. Activities were as follows and were graded by subject as 1 = always, 2 = often, 3 = sometimes, 4 = rarely, and 5 = never: 1. How often were you unable to do your work because of problems with your hand(s) / wrist(s)? 2. How often did you have to shorten your work day because of problems with your hand(s) / wrist(s)? 3. How often did you have to take it easy at your work because of problems with your hand(s) / wrist(s)? 4. How often did you accomplish less in your work because of problems with your hand(s) / wrist(s)? 5. How often did you take longer to do tasks in your work because of problems with your hand(s) / wrist(s)?

Time frame: Baseline and 3, 6, 9, and 12 months post-treatment

Population: Safety analysis set; see previously reported population description. 1 subject did not complete baseline questionnaire; 1 subject did not complete 6-month questionnaire.

Effectiveness was measured by evaluating level of satisfaction in subject's hand appearance among subjects between baseline and 3, 6, 9 and 12 months

Time frame: 3, 6, 9, and 12 months from baseline

Population: Safety analysis set, or subset of subjects exposed to study medication at least once. After 3 months, untreated controls were treated with Radiesse. All subjects (n=98) were followed to 9-months post-treatment; only the original treatment group (n=75) was followed to 12-months post-treatment. 2 subjects were enrolled \& withdrew prior to treatment.

Effectiveness was measured by evaluating subject's likelihood of return for additional Radiesse hand treatments at 3, 6, 9 and 12 months

Time frame: 3, 6, 9, and 12 months from baseline

Population: Safety analysis set, or subset of subjects exposed to study medication at least once. After 3 months, untreated controls were treated with Radiesse. All subjects (n=98) were followed to 9-months post-treatment; only the original treatment group (n=75) was followed to 12-months post-treatment. 2 subjects were enrolled \& withdrew prior to treatment.

Effectiveness was measured by evaluating level of satisfaction in subject's hand appearance among physicians between baseline and 3, 6, 9 and 12 months, by subject

Time frame: 3, 6, 9, and 12 months from baseline

Population: Safety analysis set, or subset of subjects exposed to study medication at least once. After 3 months, untreated controls were treated with Radiesse. All subjects (n=98) were followed to 9-months post-treatment; only the original treatment group (n=75) was followed to 12-months post-treatment. 2 subjects were enrolled \& withdrew prior to treatment.