A Randomized, Placebo Controlled, Double blind, Multi-centric clinical study to evaluate in use tolerance and efficacy of a topical formulation Livon Hair Gain Tonic (containing Diaminopyrimidine Oxide) in men with androgenetic alopecia (6 months study)

BriefMethodology:

It is Randomized,Placebo Controlled, Double blind, Multi-centric clinical study to evaluate inuse tolerance and efficacy of a topical formulation Livon Hair Gain Tonic(containing Diaminopyrimidine Oxide) in men with androgenetic alopecia. (6months study). The trial will be conducted in two centers in India. Product orplacebo has to be applied approximately 4-6 ml on the entire scalp twice dailyfor 6 months. The primary objectives will be to evaluate Hair re-growth/Hairloss/alopecia progression by Global Photography, Hair re-Growth/Hairloss/alopecia using Photo-trichogram, Hair loss and alopecia progression by A/TRatio, Hair growth by Anagen Hair, Hair density, Hair loss by telogen haircount and hair loss/ hair fall/ falling hair by telogen hair % onDAY-1,DAY-3,DAY-43,DAY-45,DAY-88,DAY-90,DAY-178,DAY-180. The secondaryobjectives of the study will be to evaluate efficacy of a test product VsPlacebo as per the Dermatologist on CGI-I Scale at the end of the study,efficacy of a test product Vs Placebo as per the subjects at the end of thestudy, tolerance of a test product on scalp by evaluating occurrence of any ADRlike redness, itching, swelling etc. and tolerability of a test product byevaluation of occurrence of AE/SAE at all visits from baseline to the end ofstudy.

Results:

In the present study atotal of 147 subjects were screened. There were 63 screen failures as they didnot meet the inclusion / exclusion criteria. Of these subjects, 84 subjectswere included in study and they received the study product or placebo.  A total of 14 subjects dropped out from thestudy due to loss to follow up and 70 subjects were considered as completers orefficacy evaluable cases. All the subjects who took even a single dose of thestudy drug were considered for safety evaluation. There were 34 subjects the inthe Placebo group while 36 subjects in the LHGT group who were considered asevaluable cases.

A) Age wise Distribution of subjects

The averageage of subjects in the Group A (Placebo) was 32.47 ±8.43 while in the Group B (LHGT) it was 33.33 ±8.12. There was no significant difference in the averageage of subjects in the two study groups.

**B)**Assessment of Hair re-Growth/Hair loss/alopecia progressionby change in hair density using Photo-trichogram

Therewas a significant reduction in Hair density from baseline to follow up visit atday 43 to day 178 in Group A (Placebo) whilein Group B (LHGT) there wassignificant increase in hair density levels. On analysing between the twogroups significant difference was observed where Group B (LHGT) showed asignificant increase in Hair density.

Inthe Group A (Placebo) themean Hair density was 149.85 ±42.62 at baseline which was reducedsignificantly to 132.03 ±37.68, 124.63 ±42.40 and 105.06 ±40.28 at the end of day43, day 88 and day 178 respectively. In the Group B(LHGT) the mean Hair density level atbaseline visit was 148.49 ±53.11 which increased significantly to 169.62 ±47.54, 184.12 ±49.24 and 196.67 ±49.05 at the end of day 43, day 88 and day 178respectively. At the end of study there was a decrease of 29.89% in Hairdensity in Placebo group while in LHGT group there was an increase of 32.45%over 180 days of application.

C) Assessment of TotalHair count on Photo-trichogram

It is observedthat there is a statistically significant improvement in Hair count in theGroup B (LHGT) as compared to Group A. In Group A (Placebo) themean Hair count was 108.36 ±30.39 at baseline which was reducedsignificantly to 95.25 ±27.18, 89.91 ±30.59 and 75.69 ±29.18 at the end of day 43, day 88 andday 178 respectively. In the Group B(LHGT) the mean Hair density level atbaseline visit was 107.12 ±38.32, which increased significantly to 122.35 ±34.32, 132.84 ±35.54 and 141.88 ±35.37 at the end of day 43, day 88 and day 178respectively. The hair count showed a decrease of 30.14% in Placebo group whilein LHGT group there was an increase of 32.45% over 180 days of application

D) Assessment ofHair loss/ alopecia progression by A/T Ratio

It was observed that in the Group A (Placebo) mean baselinevalue of A/T ratio was 2.65 ±0.52 which showed a significantreduction over follow up visit and was observed as 2.35±0.38, 2.24 ±0.51 and 1.90 ±0.40 at day 45, day 90 and day 180 respectively. In the Group B (LHGT)the mean A/T ratio was found to be 2.63±0.55 at baseline visit which increased significantly to 2.86 ±0.72, 3.01 ±0.88 and 3.20 ±0.96 at day 45, day 90 and day 180 respectively. Between groupsanalysis found that there was significant difference in the two groups whereGroup B (LHGT) showedsignificant increase in the AT ratio as compared to Group A (Placebo). In termsof percentage difference from baseline to 180 days there was a decrease of 28.31%in the A/T ratio in Placebo group while in the LHGT group there was a increaseof 21.47% over 180 days of application.

E) Assessment ofHair growth by Anagen % on Photo-trichogram

Inthe Group A (Placebo) the mean Anagen Hair Percentage was 72.67 ±3.94 at baseline visit which reduced to 70.13 ±3.82, 69.53 ±5.46and 65.61 ±4.67 at the endof 45, 90 and 180 days respectively. These changes were found to be significant when compared to baseline. Inthe Group B (LHGT) mean Anagen HairPercentage at the baseline was 72.42 ±4.04 which increased to 73.99 ±4.90, 75.28 ±4.98and 76.56 ±4.53 at the endof 45, 90 and 180 days respectively. These changes were found to be significantas compared to the baseline. On analysing between the two groups significantdifference was observed for Anagen Hair Percentage where there was asignificant increase in Anagen hair in Group B (LHGT) as compared to Group B (LHGT). The Anagen Hair percentage decreased by 9.72% inPlacebo group while in the LHGT group there was an increase of 5.72% frombaseline to 180 days

F) Assessment of Telogenhair % by Photo-trichogram

It was observed that in the Group A (Placebo)mean baselinevalue of Telogen percentage was 27.09 ±3.97 which showed a significantincrease over follow up visit and was observed as 29.64 ±3.83, 31.15 ±4.51 and34.42 ±4.71 at day 45, day 90 and day 180 respectively. In the Group B (LHGT)the mean Telogen percentage was foundto be 27.56 ±4.03 at baseline visit which non significantly reduced to 25.97 ±4.89, 24.71 ±4.98 and 23.43 ±4.53 at day 45, day 90 and day 180respectively. Between groups analysis found that there was significantdifference in the two groups. The difference from baseline to day 180 forTelogen hair percentage in the placebo group was an increase of 27.07% but thesame in LHGT group was a decrease of 14.98%.

G) Assessment ofHair growth rate by Photo-trichogram:

InGroup A (Placebo) the mean Hairgrowth rate was 0.86 ±0.11 at baseline visitwhich at the end of 45, 90 and 180 days were found to be 0.85 ±0.10, 0.83 ±0.14 and 0.75 ±0.13 respectively. These decreases werefound to be statistically non-significant at day 45 day 90 while on day 180 itwas found to be significant. In the Group B (LHGT) the mean Hair growth rate at baseline was 0.88 ±0.09 which showedincrease after 45 days to 0.90± 0.13, after 90 and 180 days it was found to be 0.91 ±0.13 and 0.92 ±0.16 respectively. This change in hairgrowth rate on day 45 and day 90 was found to be statistically non-significantbut on day 180 was it was found to be significant. Between groups analysisshowed non-significant difference on day 45 and day 90, while on day 180 it wasfound to be significant. There was a 12.98% decrease in hair growth rate ascompared to baseline in Placebo group while in the LHGT group there was anincrease of 5.33% over 180 days of application.

H) Assessment ofHair re-growth/Hair loss/alopecia progression by Global Photography

Assessment of hair growth overGlobal photography at Frontal, Vertex and Overall (Total) revealed that therewas no significant difference between the two groups when compared at day 45. Therewas a significant difference between the group for Vertex and overall (Total)score on day 90 and day 180. The mean score of Global photography for frontalarea in placebo group was 0.85 ±0.66, 0.71 ±0.63,and 0.91 ±0.75 on day 45, day 90 and day 180 respectively. While in the LHGT groupit was 0.86 ±0.80, 0.92 ±0.84, and 1.11 ±0.95 on day 45, day 90and day 180 respectively, these were found to be significant. At the vertex on day 45, day 90and day 180 this scores were 0.68 ±0.73, 0.62 ±0.65, 0.56 ±0.66 respectively in placebo groupwhich in the LHGT group were found to be 0.61 ±0.77, 0.83 ±0.97, 1.08 ±0.73 respectively, thesewere found to be significant. Similarly the overall (Total) scores in placebo group were 1.53 ±1.38, 1.32 ±1.28, and 1.47 ±1.41 on day 45, day 90 and day 180 respectively. While in the LHGT group it were1.47 ±1.56, 1.75 ±1.81, 2.19, ±1.68, these values werefound to be significant.

Assessment of hair density overGlobal photography at Frontal, Vertex and Overall (Total) revealed that therewas no significant difference between the two groups when compared at day 45and day 90. The mean scores of Global photography for frontal area on day 45,day 90 and day 180 in placebo group were 0.85 ±1.05, 0.82 ±0.97, 0.97 ±0.63 respectively which in the LHGT group were 1.03 ±1.06, 1.17 ±0.70, 1.06 ±0.89. At the vertex on day 45, day 90 and day 180 thesescores were 0.71 ±0.97, 0.82 ±0.76, 0.44 ±0.66 in placebo group which in theLHGT group were found to be 0.92 ±0.97, 0.94 ±0.86, 1.08 ±0.73. Similarly the overall (Total)scores on day 45, day 90 and day 180 in placebo group were 1.56 ±2.02, 1.65 ±1.73, 1.41 ±1.29 respectively while in the LHGT group these were 1.94±2.02, 2.11±1.56, 2.14 ±1.62

I) Assessment of efficacy of test product by Physicians onCGI scale.

In Placebo group, 9 subjects showedminimal improvement in hair growth while 10 subject’s shows no change. 15subjects show minimal to much worse hair growth on day 180 as compared tobaseline visit.

In LHGT group, 14 subjects showedmuch improvement in hair growth while 16 subjects showed minimal improvement. 3subjects showed no change in hair growth where at the same time 2 subjects’sshowed minimal worsening on day 180 as compared to baseline visit

**J)**Assessment of tolerability of a test product by evaluationof occurrence of AE/SAE

None of the AE was related to the study drug or procedure. No treatment or interruption of thestudy drug or procedure was required to resolve these episodes.

K) Effect of study drug on Vitals:

There was no significant change inthese parameters from baseline to every follow up visit till the end of studyi.e. 180 days.

Conclusion:

Thepresent study concludes that regular application of LHGT significantly improveshair growth and density as observed from Phototrichogram evaluation. A gradualand constant increase in hair density and growth was observed over a period of180 days starting from as early as 45 days. Non application (Placebo) showedsignificant decrease on both hair growth and density.

Therewas a significant reduction in hair loss/alopecia progression as observed onA/T ratio with the use of LHGT over 180 days starting from day 45. The hairloss/alopecia also showed constant and continuous increase (worsening) innon-users (placebo).

Significantincrease in Anagen% and reduction in Telogen % was also observed in LHGT group,which was reverse in the placebo group, thus signifying the potential hairbenefit of LHGT. Hair growth rate also showed a significantly better change ascompared to non-users (placebo).

Theabove changes were observed on instrumental analysis as early as 45 days whilethe clinical and global photographic changes were seen at 3 months to 6 monthsfollow ups.

Physician’s(dermatologists) global evaluation also showed that a majority of subjectsshowing significant improvement with the use of LHGT.

LHGTwas well tolerated and did not show any adverse effect on its regularapplication for 6 months duration.

LHGT can berecommended as a safe and effective remedy in the treatment of men sufferingfrom Androgenic Alopecia.