Trial Outcomes & Findings for A Study to Assess the Effects of an Oral Dietary Supplement on Overall Facial Appearance Among Healthy Adult Women With Existing Skin Damage From Sun Exposure (NCT NCT01787461)

Last Updated: 2015-03-18

Results Overview

IGA of overall facial appearance was measured using a numerical severity rating scale of 0 to 9 using 1/2 points, where 0 to less than or equal to (\<=) 3 signifies Mild; greater than (\>) 3 to \<=6 signifies Moderate and \>6 to \<=9 signifies Severe.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

194 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2015-03-18

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Overall Study STARTED	96	98
Overall Study COMPLETED	82	89
Overall Study NOT COMPLETED	14	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Overall Study Adverse Event	4	3
Overall Study Lost to Follow-up	3	2
Overall Study No longer met eligibility criteria	1	0
Overall Study Withdrawal by Subject	3	4
Overall Study Protocol Violation	3	0

Baseline Characteristics

A Study to Assess the Effects of an Oral Dietary Supplement on Overall Facial Appearance Among Healthy Adult Women With Existing Skin Damage From Sun Exposure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=95 Participants Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=98 Participants Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.	Total n=193 Participants Total of all reporting groups
Age, Continuous	52.5 years STANDARD_DEVIATION 7.38 • n=99 Participants	52.7 years STANDARD_DEVIATION 6.58 • n=107 Participants	52.6 years STANDARD_DEVIATION 6.96 • n=206 Participants
Sex: Female, Male Female	95 Participants n=99 Participants	98 Participants n=107 Participants	193 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Modified intent-to-treat (m-ITT) population included all randomized participants who had at least 1 pre-dose and post-dose assessment value. Here "n" signifies those participants who were evaluable for this measure at specified time- points for each arm, respectively.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=97 Participants Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Change From Baseline in Investigator Global Assessment (IGA) of Participant's Overall Facial Appearance at Week 24 Baseline (n=93,97)	6.04 units on scale Standard Deviation 1.45	5.81 units on scale Standard Deviation 1.30
Change From Baseline in Investigator Global Assessment (IGA) of Participant's Overall Facial Appearance at Week 24 Change at Week 24 (n=92,95)	0.6 units on scale Standard Deviation 1.28	0.7 units on scale Standard Deviation 1.23

SECONDARY outcome

Timeframe: Week 24

Population: m-ITT population included all randomized participants who had at least 1 pre-dose and post-dose assessment value. Here "N" (number of participants analyzed) signifies those participants who were evaluable for this measure.

IPRC assessment was performed in accordance with the Canfield procedures and rated the improvement relative to Baseline. The investigators used an improvement scale that ranged from -3 to 3 (where -3 = Definite worsening, -2 = Moderate worsening, -1 = Slight worsening, 0 = No change, 1 = Slight improvement, 2 = Moderate improvement, 3 = Definite improvement).

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=94 Participants Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Photographic Assessment Compared to Baseline of the Participants Overall Facial Appearance by Independent Panel Review Committee (IPRC) at Week 24	-0.2 units on scale Standard Deviation 0.86	-0.1 units on scale Standard Deviation 0.82

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: m-ITT population included all randomized participants who had at least 1 pre-dose and post-dose assessment value. Here "n" signifies those participants who were evaluable for this measure at specified time- points for each arm, respectively.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=97 Participants Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Change From Baseline in Investigator Global Assessment (IGA) of Participant's Overall Facial Appearance at Week 12 Baseline (n=93,97)	6.04 units on scale Standard Deviation 1.45	5.81 units on scale Standard Deviation 1.30
Change From Baseline in Investigator Global Assessment (IGA) of Participant's Overall Facial Appearance at Week 12 Change at Week 12 (n=92,95)	0.4 units on scale Standard Deviation 1.14	0.4 units on scale Standard Deviation 1.07

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Investigator performed the assessment of face (Fine lines/wrinkles (L/W) of the periocular area (A), Fine lines/wrinkles of the perioral area, dark circles (dc) or "bags" under the eye, mottled hyperpigmentation (MH), sallowness/yellowing, roughness/texture) using a numerical severity rating scale of 0 to 9, where 0 to less than or equal to (\<=) 3 signifies Mild; greater than (\>) 3 to \<=6 signifies Moderate and \>6 to \<=9 signifies Severe.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=97 Participants Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Baseline: Fine L/W Periocular A (n=93,97)	5.95 units on scale Standard Deviation 1.50	5.79 units on scale Standard Deviation 1.44
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Baseline: Fine L/W Perioral A (n= 93,97)	4.89 units on scale Standard Deviation 1.78	4.69 units on scale Standard Deviation 1.65
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Baseline: Under eye dc or bags(n= 93,97)	5.68 units on scale Standard Deviation 1.55	5.34 units on scale Standard Deviation 1.44
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Baseline: MH (n=93,97)	4.95 units on scale Standard Deviation 1.71	5.06 units on scale Standard Deviation 1.51
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Baseline: Sallowness/yellowing (n=93,97)	3.41 units on scale Standard Deviation 1.42	3.51 units on scale Standard Deviation 1.33
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Baseline: Roughness/texture (n=93,97)	3.10 units on scale Standard Deviation 1.66	2.77 units on scale Standard Deviation 1.50
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Change at Week 12: Fine L/W Periocular A(n= 92,95)	0.5 units on scale Standard Deviation 1.04	0.5 units on scale Standard Deviation 1.09
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Change at Week 12: Fine L/W Perioral A(n= 92,95)	0.4 units on scale Standard Deviation 1.01	0.4 units on scale Standard Deviation 1.07
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Change at Week 12: Under eye dc or bags (n= 92,95)	0.5 units on scale Standard Deviation 1.28	0.3 units on scale Standard Deviation 1.38
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Change at Week 12: MH (n= 92,95)	0.3 units on scale Standard Deviation 1.38	0.3 units on scale Standard Deviation 1.42
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Change at Week 12: Sallowness/yellowing (n= 92,95)	0.4 units on scale Standard Deviation 1.46	0.4 units on scale Standard Deviation 1.45
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Change at Week 12: Roughness/texture (n= 92,95)	0.4 units on scale Standard Deviation 1.63	0.2 units on scale Standard Deviation 1.45
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Change at Week 24: Fine L/W Periocular A(n= 92,95)	0.7 units on scale Standard Deviation 1.31	0.8 units on scale Standard Deviation 1.26
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Change at Week 24: Fine L/W Perioral A(n= 92,95)	0.4 units on scale Standard Deviation 1.14	0.5 units on scale Standard Deviation 1.09
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Change at Week 24: Under eye dc or bags (n= 92,95)	0.7 units on scale Standard Deviation 1.66	0.6 units on scale Standard Deviation 1.37
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Change at Week 24: MH (n= 92,95)	0.7 units on scale Standard Deviation 1.32	0.7 units on scale Standard Deviation 1.36
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Change at Week 24: Sallowness/yellowing (n= 92,95)	1.0 units on scale Standard Deviation 1.43	1.0 units on scale Standard Deviation 1.45
Change From Baseline in Investigator Assessment of Face at Weeks 12 and 24 Change at Week 24: Roughness/texture (n= 92,95)	0.8 units on scale Standard Deviation 1.65	0.5 units on scale Standard Deviation 1.63

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Investigator performed the assessment of decolletage and back of hands (crepyness, mottled hyperpigmentation \[MH\]) using a numerical severity rating scale of 0 to 9 using 1/2 points, where 0 to less than or equal to (\<=) 3 signifies Mild; greater than (\>) 3 to \<=6 signifies Moderate and \>6 to \<=9 signifies Severe.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=97 Participants Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Change From Baseline in Investigator Assessment of Decolletage and Back of Hands at Weeks 12 and 24 Baseline: Decolletage-Crepyness (n=93,97)	4.65 units on scale Standard Deviation 1.77	4.56 units on scale Standard Deviation 1.60
Change From Baseline in Investigator Assessment of Decolletage and Back of Hands at Weeks 12 and 24 Baseline: Decolletage-MH (n=93,97)	5.09 units on scale Standard Deviation 1.80	5.08 units on scale Standard Deviation 1.65
Change From Baseline in Investigator Assessment of Decolletage and Back of Hands at Weeks 12 and 24 Baseline: Back of Hands-Crepyness (n=93,97)	5.37 units on scale Standard Deviation 1.43	5.19 units on scale Standard Deviation 1.42
Change From Baseline in Investigator Assessment of Decolletage and Back of Hands at Weeks 12 and 24 Baseline: Back of Hands-MH (n=93,97)	3.96 units on scale Standard Deviation 1.53	3.92 units on scale Standard Deviation 1.69
Change From Baseline in Investigator Assessment of Decolletage and Back of Hands at Weeks 12 and 24 Change at Week 12: Decolletage-Crepyness (n=92,95)	0.2 units on scale Standard Deviation 1.23	0.2 units on scale Standard Deviation 1.49
Change From Baseline in Investigator Assessment of Decolletage and Back of Hands at Weeks 12 and 24 Change at Week 12: Decolletage-MH (n=92,95)	0.4 units on scale Standard Deviation 1.36	0.5 units on scale Standard Deviation 1.20
Change From Baseline in Investigator Assessment of Decolletage and Back of Hands at Weeks 12 and 24 Change at Week 12:Back of Hands-Crepyness(n=92,95)	0.6 units on scale Standard Deviation 1.39	0.5 units on scale Standard Deviation 1.48
Change From Baseline in Investigator Assessment of Decolletage and Back of Hands at Weeks 12 and 24 Change at Week 12: Back of Hands-MH (n=92,95)	-0.2 units on scale Standard Deviation 1.09	0.3 units on scale Standard Deviation 1.08
Change From Baseline in Investigator Assessment of Decolletage and Back of Hands at Weeks 12 and 24 Change at Week 24: Decolletage-Crepyness (n=92,95)	0.7 units on scale Standard Deviation 1.56	0.7 units on scale Standard Deviation 1.36
Change From Baseline in Investigator Assessment of Decolletage and Back of Hands at Weeks 12 and 24 Change at Week 24: Decolletage-MH (n=92,95)	0.6 units on scale Standard Deviation 1.43	0.6 units on scale Standard Deviation 1.14
Change From Baseline in Investigator Assessment of Decolletage and Back of Hands at Weeks 12 and 24 Change at Week 24:Back of Hands-Crepyness(n=92,95)	0.7 units on scale Standard Deviation 1.39	0.7 units on scale Standard Deviation 1.45
Change From Baseline in Investigator Assessment of Decolletage and Back of Hands at Weeks 12 and 24 Change at Week 24: Back of Hands-MH (n=92,95)	0.1 units on scale Standard Deviation 1.20	0.4 units on scale Standard Deviation 1.22

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Participants performed the assessment of face (overall facial (OA) appearance, fine lines and wrinkles (L/W) present in the eye area, upper lip, or cheek areas, under eye dark circles (dc) or bags, discoloration \[uneven, patchy, blotchy areas of light and dark, age spots, liver spots\], complexion/glow \[bright radiant appearance\] and smoothness) at Baseline using a 10-point numerical scale, and at Week 12, 24 using a 7-point improvement scale. At Baseline, participants rated the facial parameters using a 10-point scale ranging from 1 (Not noticeable) to 10 (Very noticeable). At Week 12 and 24, assessment was performed relative to Baseline using an improvement scale that ranged from -3 to 3 (where -3 = Definite worsening, -2 = Moderate worsening, -1 = Slight worsening, 0 = No change, 1 = Slight improvement, 2 = Moderate improvement, 3 = Definite improvement).

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=97 Participants Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Participants Improvement Assessment of Face at Week 12 and 24 Baseline: OA of facial skin (n=93,97)	5.67 units on scale Standard Deviation 1.83	5.60 units on scale Standard Deviation 1.62
Participants Improvement Assessment of Face at Week 12 and 24 Baseline: Fine L/W (n=93,97)	6.51 units on scale Standard Deviation 2.11	6.46 units on scale Standard Deviation 1.89
Participants Improvement Assessment of Face at Week 12 and 24 Baseline: Under eye dc or bags (n=93,97)	5.80 units on scale Standard Deviation 2.66	5.82 units on scale Standard Deviation 2.64
Participants Improvement Assessment of Face at Week 12 and 24 Baseline: Discoloration (n=93,97)	5.85 units on scale Standard Deviation 2.42	6.59 units on scale Standard Deviation 2.23
Participants Improvement Assessment of Face at Week 12 and 24 Baseline: Complexion/Glow (n=93,97)	5.19 units on scale Standard Deviation 2.00	5.02 units on scale Standard Deviation 1.75
Participants Improvement Assessment of Face at Week 12 and 24 Baseline: Smoothness (n=93,97)	6.69 units on scale Standard Deviation 1.92	6.49 units on scale Standard Deviation 1.86
Participants Improvement Assessment of Face at Week 12 and 24 Improvement Week 12: OA of facial skin (n=92,96)	0.7 units on scale Standard Deviation 1.06	0.8 units on scale Standard Deviation 0.92
Participants Improvement Assessment of Face at Week 12 and 24 Improvement Week 12: Fine L/W (n=92,96)	0.4 units on scale Standard Deviation 0.84	0.6 units on scale Standard Deviation 0.89
Participants Improvement Assessment of Face at Week 12 and 24 Improvement Week 12: Under eye dc or bags(n=92,96)	0.3 units on scale Standard Deviation 0.72	0.3 units on scale Standard Deviation 0.95
Participants Improvement Assessment of Face at Week 12 and 24 Improvement Week 12: Discoloration (n=91,95)	0.3 units on scale Standard Deviation 0.80	0.4 units on scale Standard Deviation 1.01
Participants Improvement Assessment of Face at Week 12 and 24 Improvement Week 12: Complexion/Glow (n=92,96)	0.7 units on scale Standard Deviation 0.83	0.7 units on scale Standard Deviation 0.86
Participants Improvement Assessment of Face at Week 12 and 24 Improvement Week 12: Smoothness (n=92,96)	0.9 units on scale Standard Deviation 1.01	1.0 units on scale Standard Deviation 0.97
Participants Improvement Assessment of Face at Week 12 and 24 Improvement Week 24: OA of facial skin (n=92,96)	0.8 units on scale Standard Deviation 1.23	1.0 units on scale Standard Deviation 1.26
Participants Improvement Assessment of Face at Week 12 and 24 Improvement Week 24: Fine L/W (n=92,96)	0.6 units on scale Standard Deviation 1.01	0.8 units on scale Standard Deviation 1.18
Participants Improvement Assessment of Face at Week 12 and 24 Improvement Week 24: Under eye dc or bags(n=92,96)	0.4 units on scale Standard Deviation 0.88	0.5 units on scale Standard Deviation 1.08
Participants Improvement Assessment of Face at Week 12 and 24 Improvement Week 24: Discoloration (n=91,93)	0.3 units on scale Standard Deviation 0.97	0.5 units on scale Standard Deviation 1.11
Participants Improvement Assessment of Face at Week 12 and 24 Improvement Week 24: Complexion/Glow (n=92,96)	0.8 units on scale Standard Deviation 1.16	0.9 units on scale Standard Deviation 1.12
Participants Improvement Assessment of Face at Week 12 and 24 Improvement Week 24: Smoothness (n=92,96)	1.1 units on scale Standard Deviation 1.22	1.2 units on scale Standard Deviation 1.13

SECONDARY outcome

Timeframe: Baseline, Week 12, 24

Participants performed the assessment of decolletage (decolletage overall, decolletage-wrinkling/crinkling (W/C), decolletage-discoloration (DD) and back of hands (back of hands overall, back of hands (BOH) - Fine lines/wrinkles (L/W), back of hands - discoloration) and Body - Dryness (BD) Overall at baseline using a 10-point numerical scale, and at Week 12, 24 using a 7-point improvement scale. At Baseline, participants rated the Decolletage, Back of Hands and Body parameters using a 10-point scale ranging from 1 (Not noticeable) to 10 (Very noticeable). At Week 12 and 24, assessment was performed relative to Baseline using an improvement scale that ranged from -3 to 3 (where -3 = Definite worsening, -2 = Moderate worsening, -1 = Slight worsening, 0 = No change, 1 = Slight improvement, 2 = Moderate improvement, 3 = Definite improvement).

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=97 Participants Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Baseline: Decolletage-Overall (n=93,97)	5.34 units on scale Standard Deviation 2.08	5.19 units on scale Standard Deviation 1.92
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Baseline: Decolletage-W/C (n=93,97)	5.59 units on scale Standard Deviation 2.35	5.48 units on scale Standard Deviation 2.22
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Baseline: Decolletage-Discoloration (n=93,97)	5.88 units on scale Standard Deviation 2.59	6.06 units on scale Standard Deviation 2.21
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Baseline: Back of Hands-Overall (n=93,97)	4.89 units on scale Standard Deviation 2.15	4.89 units on scale Standard Deviation 1.98
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Baseline: Back of Hands - Fine L/W (n=93,97)	6.23 units on scale Standard Deviation 2.56	6.53 units on scale Standard Deviation 2.25
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Baseline: Back of Hands - Discoloration (n=93,97)	5.91 units on scale Standard Deviation 2.62	5.83 units on scale Standard Deviation 2.56
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Baseline: Body - Dryness Overall (n=93,97)	5.34 units on scale Standard Deviation 2.23	5.15 units on scale Standard Deviation 2.03
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 12: Decolletage-Overall (n=92,96)	0.3 units on scale Standard Deviation 0.70	0.5 units on scale Standard Deviation 0.75
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 12: Decolletage-W/C (n=92,96)	0.2 units on scale Standard Deviation 0.67	0.4 units on scale Standard Deviation 0.78
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 12: DD (n=87,94)	0.1 units on scale Standard Deviation 0.57	0.3 units on scale Standard Deviation 0.69
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 12: BOH-Overall (n=92,96)	0.3 units on scale Standard Deviation 0.68	0.4 units on scale Standard Deviation 0.92
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 12: BOH - Fine L/W (n=92,96)	0.2 units on scale Standard Deviation 0.65	0.4 units on scale Standard Deviation 0.90
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 12: BOH - Discoloration (n=88,94)	0.2 units on scale Standard Deviation 0.69	0.3 units on scale Standard Deviation 0.82
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 12: BD Overall (n=91,96)	0.6 units on scale Standard Deviation 0.96	0.5 units on scale Standard Deviation 1.06
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 24: Decolletage-Overall (n=92,96)	0.5 units on scale Standard Deviation 1.00	0.7 units on scale Standard Deviation 1.03
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 24: Decolletage-W/C (n=92,96)	0.5 units on scale Standard Deviation 0.94	0.7 units on scale Standard Deviation 0.98
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 24: DD (n=88,91)	0.3 units on scale Standard Deviation 0.90	0.6 units on scale Standard Deviation 1.08
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 24:BOH-Overall (n=92,96)	0.5 units on scale Standard Deviation 0.99	0.7 units on scale Standard Deviation 1.08
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 24: BOH - Fine L/W (n=92,96)	0.4 units on scale Standard Deviation 0.93	0.6 units on scale Standard Deviation 1.02
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 24: BOH - Discoloration (n=91,91)	0.3 units on scale Standard Deviation 0.94	0.5 units on scale Standard Deviation 0.97
Participant Improvement Assessment of Decolletage, Back of Hands and Body at Week 12 and 24 Improvement Week 24: BD Overall (n=92,96)	0.7 units on scale Standard Deviation 1.13	0.7 units on scale Standard Deviation 1.18

SECONDARY outcome

Timeframe: Baseline, Week 6, 12, 18, 24

DermaLab Combo Skin Lab with an 8-pin probe was used to measure hydration (corneometry). Hydration measurements of the left cheek, left inner arm, and left outer arm were taken (up to 3 measurement).

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=97 Participants Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Baseline: Left Cheek (n=93,97)	231.7 microsecond Standard Deviation 54.58	238.7 microsecond Standard Deviation 69.69
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Change at Week 6: Left Cheek (n=93,97)	-5.2 microsecond Standard Deviation 48.13	1.9 microsecond Standard Deviation 70.39
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Change at Week 12: Left Cheek (n=87,92)	16.7 microsecond Standard Deviation 52.70	20.0 microsecond Standard Deviation 69.01
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Change at Week 18: Left Cheek (n=85,91)	35.1 microsecond Standard Deviation 47.03	35.5 microsecond Standard Deviation 70.18
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Change at Week 24: Left Cheek (n=85,91)	33.1 microsecond Standard Deviation 53.86	29.1 microsecond Standard Deviation 71.44
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Baseline: Left Inner Arm (n=93,97)	150.0 microsecond Standard Deviation 41.37	157.2 microsecond Standard Deviation 52.72
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Change at Week 6: Left Inner Arm (n=93,97)	-10.6 microsecond Standard Deviation 48.51	-3.7 microsecond Standard Deviation 54.36
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Change at Week 12: Left Inner Arm (n=87,92)	-5.2 microsecond Standard Deviation 69.84	4.4 microsecond Standard Deviation 61.24
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Change at Week 18: Left Inner Arm (n=85,91)	15.3 microsecond Standard Deviation 45.69	15.7 microsecond Standard Deviation 55.30
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Change at Week 24: Left Inner Arm (n=85,91)	15.4 microsecond Standard Deviation 39.36	12.0 microsecond Standard Deviation 53.89
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Baseline: Left Outer Arm (n=93,97)	120.0 microsecond Standard Deviation 49.37	130.0 microsecond Standard Deviation 61.83
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Change at Week 6: Left Outer Arm (n=93,97)	-6.4 microsecond Standard Deviation 42.13	-3.5 microsecond Standard Deviation 57.26
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Change at Week 12: Left Outer Arm (n=87,92)	-1.5 microsecond Standard Deviation 45.13	1.7 microsecond Standard Deviation 57.49
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Change at Week 18: Left Outer Arm (n=85,91)	9.8 microsecond Standard Deviation 45.27	14.0 microsecond Standard Deviation 58.47
Change From Baseline in Skin Hydration at Week 6, 12, 18 and 24 Change at Week 24: Left Outer Arm (n=85,91)	9.4 microsecond Standard Deviation 48.60	10.2 microsecond Standard Deviation 50.92

SECONDARY outcome

Timeframe: Baseline, Week 6, 12, 18, 24

Trans-epidermal water loss (TEWL) measurements were done using DermaLab Combo SkinLab with a cylindrical diffusion chamber (10 mm \[millimeter\] diameter) containing 2 combined humidity/temperature sensors to determine the amount of water vapor that moves across the stratum corneum. TEWL measurements were taken on the left cheek and the left inner and outer arm (up to 3 measurement).

Outcome measures

SECONDARY outcome

Timeframe: Baseline, Week 6, 12, 18, 24

Skin thickness was measured using the DUB Cutis (taberna pro medicum), a high frequency and high resolution diagnostic ultrasound system. Measurements were taken on the left cheek, and the left inner and outer arm (up to 3 measurement).

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=97 Participants Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Baseline: Left Cheek (n=93,97)	1568.2 micrometer Standard Deviation 234.01	1531.1 micrometer Standard Deviation 243.04
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Change at Week 6: Left Cheek (n=89,95)	2.4 micrometer Standard Deviation 169.50	-33.9 micrometer Standard Deviation 164.03
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Change at Week 12: Left Cheek (n=87,92)	11.3 micrometer Standard Deviation 167.01	-37.1 micrometer Standard Deviation 169.86
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Change at Week 18: Left Cheek (n=84,90)	-21.7 micrometer Standard Deviation 173.71	-45.8 micrometer Standard Deviation 169.60
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Change at Week 24: Left Cheek (n=82,90)	-55.6 micrometer Standard Deviation 225.02	-81.1 micrometer Standard Deviation 230.14
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Baseline: Left Inner Arm (n=93,96)	1101.8 micrometer Standard Deviation 159.25	1076.4 micrometer Standard Deviation 137.32
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Change at Week 6: Left Inner Arm (n=91,96)	4.7 micrometer Standard Deviation 94.41	3.0 micrometer Standard Deviation 86.69
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Change at Week 12: Left Inner Arm (n=87,91)	-11.1 micrometer Standard Deviation 102.32	-15.6 micrometer Standard Deviation 92.83
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Change at Week 18: Left Inner Arm (n=84,88)	-16.6 micrometer Standard Deviation 117.88	-43.2 micrometer Standard Deviation 108.18
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Change at Week 24: Left Inner Arm (n=82,89)	-73.2 micrometer Standard Deviation 126.50	-66.6 micrometer Standard Deviation 126.87
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Baseline: Left Outer Arm (n=93,96)	1349.4 micrometer Standard Deviation 191.23	1332.2 micrometer Standard Deviation 169.61
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Change at Week 6: Left Outer Arm (n=92,96)	9.1 micrometer Standard Deviation 106.38	17.0 micrometer Standard Deviation 100.85
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Change at Week 12: Left Outer Arm (n=87,91)	9.5 micrometer Standard Deviation 101.58	5.2 micrometer Standard Deviation 95.81
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Change at Week 18: Left Outer Arm (n=84,89)	-3.3 micrometer Standard Deviation 117.71	-23.1 micrometer Standard Deviation 120.42
Change From Baseline in Skin Thickness at Week 6, 12,18 and 24 Change at Week 24: Left Outer Arm (n=82,89)	-55.3 micrometer Standard Deviation 144.09	-55.3 micrometer Standard Deviation 135.32

SECONDARY outcome

Timeframe: Baseline, Week 6, 12, 18, 24

Skin density was measured using the DUB Cutis (taberna pro medicum), a high frequency and high resolution diagnostic ultrasound system with 100 percent (%) calibration mode. Measurements were taken on the left cheek, and the left inner and outer arm (up to 3 measurement).

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=97 Participants Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Baseline: Left Cheek (n=58,59)	10.5 micrometer Standard Deviation 4.05	10.3 micrometer Standard Deviation 3.78
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Change at Week 6: Left Cheek (n=57,59)	-0.1 micrometer Standard Deviation 4.43	-0.7 micrometer Standard Deviation 5.13
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Change at Week 12: Left Cheek (n=54,55)	-0.1 micrometer Standard Deviation 4.49	-0.8 micrometer Standard Deviation 4.34
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Change at Week 18: Left Cheek (n=49,52)	-1.8 micrometer Standard Deviation 5.68	-3.3 micrometer Standard Deviation 6.22
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Change at Week 24: Left Cheek (n=49,53)	-2.5 micrometer Standard Deviation 5.68	-3.3 micrometer Standard Deviation 5.42
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Baseline: Left Inner Arm (n=58,58)	28.0 micrometer Standard Deviation 6.96	29.2 micrometer Standard Deviation 8.41
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Change at Week 6: Left Inner Arm (n=57,58)	-1.0 micrometer Standard Deviation 10.20	1.2 micrometer Standard Deviation 11.61
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Change at Week 12: Left Inner Arm (n=54,54)	0.3 micrometer Standard Deviation 8.73	-0.7 micrometer Standard Deviation 10.05
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Change at Week 18: Left Inner Arm (n=49,50)	-4.5 micrometer Standard Deviation 10.73	-4.6 micrometer Standard Deviation 13.87
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Change at Week 24: Left Inner Arm (n=49,52)	-6.6 micrometer Standard Deviation 10.98	-4.9 micrometer Standard Deviation 11.64
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Baseline: Left Outer Arm (n=58,58)	19.5 micrometer Standard Deviation 5.82	19.4 micrometer Standard Deviation 6.66
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Change at Week 6: Left Outer Arm (n=58,58)	-0.2 micrometer Standard Deviation 7.47	0.0 micrometer Standard Deviation 7.75
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Change at Week 12: Left Outer Arm (n=54,54)	-0.5 micrometer Standard Deviation 6.61	-2.0 micrometer Standard Deviation 7.93
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Change at Week 18: Left Outer Arm (n=49,51)	-2.6 micrometer Standard Deviation 9.01	-3.6 micrometer Standard Deviation 10.10
Change From Baseline in Skin Density at Week 6, 12, 18 and 24 (With 100% Calibration Mode) Change at Week 24: Left Outer Arm (n=49,52)	-4.5 micrometer Standard Deviation 9.45	-3.9 micrometer Standard Deviation 9.69

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Imedeen

Serious events: 2 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=95 participants at risk Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=98 participants at risk Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Vascular disorders Thrombosis	0.00% 0/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	1.0% 1/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	1.0% 1/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=93 Participants Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=97 Participants Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Baseline: Left Cheek (n=93,97)	11.7 gram per square meter per hour Standard Deviation 5.27	11.0 gram per square meter per hour Standard Deviation 5.04
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Change at Week 6: Left Cheek (n=93,97)	-0.0 gram per square meter per hour Standard Deviation 5.21	0.4 gram per square meter per hour Standard Deviation 4.34
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Change at Week 12: Left Cheek (n=87,92)	0.0 gram per square meter per hour Standard Deviation 3.72	0.8 gram per square meter per hour Standard Deviation 4.71
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Change at Week 18: Left Cheek (n=85,91)	0.2 gram per square meter per hour Standard Deviation 3.84	0.8 gram per square meter per hour Standard Deviation 4.35
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Change at Week 24: Left Cheek (n=85,91)	-0.4 gram per square meter per hour Standard Deviation 4.15	0.4 gram per square meter per hour Standard Deviation 4.29
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Baseline: Left Inner Arm (n=93,97)	4.8 gram per square meter per hour Standard Deviation 2.00	4.4 gram per square meter per hour Standard Deviation 1.90
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Change at Week 6: Left Inner Arm (n=93,97)	-0.3 gram per square meter per hour Standard Deviation 1.86	-0.3 gram per square meter per hour Standard Deviation 2.46
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Change at Week 12: Left Inner Arm (n=87,92)	-0.1 gram per square meter per hour Standard Deviation 1.79	0.1 gram per square meter per hour Standard Deviation 1.67
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Change at Week 18: Left Inner Arm (n=85,91)	-0.1 gram per square meter per hour Standard Deviation 1.41	0.0 gram per square meter per hour Standard Deviation 1.80
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Change at Week 24: Left Inner Arm (n=85,91)	-0.4 gram per square meter per hour Standard Deviation 1.63	-0.2 gram per square meter per hour Standard Deviation 1.72
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Baseline: Left Outer Arm (n=93,97)	4.6 gram per square meter per hour Standard Deviation 1.98	4.1 gram per square meter per hour Standard Deviation 1.57
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Change at Week 6: Left Outer Arm (n=93,97)	-0.2 gram per square meter per hour Standard Deviation 1.38	-0.2 gram per square meter per hour Standard Deviation 1.81
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Change at Week 12: Left Outer Arm (n=87,92)	-0.1 gram per square meter per hour Standard Deviation 1.53	-0.2 gram per square meter per hour Standard Deviation 1.67
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Change at Week 18: Left Outer Arm (n=85,91)	-0.0 gram per square meter per hour Standard Deviation 1.39	-0.1 gram per square meter per hour Standard Deviation 1.72
Change From Baseline in Trans-Epidermal Water Loss (TEWL) at Week 6, 12, 18 and 24 Change at Week 24: Left Outer Arm (n=85,91)	-0.4 gram per square meter per hour Standard Deviation 1.64	-0.4 gram per square meter per hour Standard Deviation 1.49

Measure	Placebo n=95 participants at risk Two Placebo tablets matched to Imedeen, orally daily for 24 weeks.	Imedeen n=98 participants at risk Imedeen (two tablets) containing marine complex at 210 (milligrams) mg, vitamin C at 48 mg, zinc at 3.6 g and tomato fruit and grape extract blend at 56 mg, orally daily for 24 weeks.
Gastrointestinal disorders Diarrhoea	1.1% 1/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	2.0% 2/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Nausea	3.2% 3/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	4.1% 4/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Vomiting	2.1% 2/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	1.0% 1/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Infections and infestations Gastroenteritis	3.2% 3/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	1.0% 1/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Infections and infestations Nasopharyngitis	3.2% 3/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	8.2% 8/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Infections and infestations Tooth infection	0.00% 0/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	2.0% 2/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Infections and infestations Upper respiratory tract infection	4.2% 4/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	3.1% 3/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Limb injury	0.00% 0/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	2.0% 2/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	2.0% 2/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Procedural pain	3.2% 3/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	2.0% 2/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Back pain	3.2% 3/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	1.0% 1/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	2.0% 2/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Nervous system disorders Headache	3.2% 3/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	1.0% 1/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Psychiatric disorders Depression	0.00% 0/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	3.1% 3/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.2% 3/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	2.0% 2/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Sinus congestion	1.1% 1/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	2.0% 2/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Acne	1.1% 1/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	2.0% 2/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.1% 5/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Erythema	2.1% 2/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Pruritus	2.1% 2/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	1.0% 1/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Rash	3.2% 3/95 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/98 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.