Chemotherapy-Induced Alopecia
Conditions
Keywords
alopecia
Brief summary
The goal of this clinical trial is to learn if Compound 31543 (topical calcitriol) for treatment of hair-loss in patients with a diagnosis of breast cancer, gynecologic cancer or sarcomas receiving a taxane-based chemotherapy is safe. The main questions it aims to answer are: * What medical problems do participants have when using compound 31543? * How much Compound 31543 is in blood after treatment? * How much hair is lost during treatment? Participants will: * Apply Compound 31543 to their scalp twice a day, starting at least 5 days before starting chemotherapy for at least 3 months or until chemotherapy treatment is completed. * Have blood drawn on weeks 1, 5, 9, 13, and 54. * Have photographs taken of their hair before starting and at weeks 7, 15, 27, and 54. * Keep a diary of the condition of their hair.
Detailed description
This was a multi-center, single arm, dose-escalation Phase 1 study to determine the maximum tolerated dose (MTD), PK, and the overall safety and tolerability of Compound 31543 in patients with a diagnosis of early-stage or locally advanced, unresectable and/or metastatic cancer, or patients with operable cancer, who were scheduled to receive follow up treatment with a taxane-based chemotherapy regimen, as per the physician's discretion. A standard 3+3 dose escalation design was employed, over 6 dose levels, with 3 to 6 patients at each dose level. Eligible patients in each cohort, \>18 years of age and scheduled to receive a taxane-based regimen with treatment breaks as per physician's discretion, initially received or applied the topical formulation of Compound 31543 to the scalp twice daily either for 2 weeks or 7 ± 2 days (if the patient was unable or unwilling to undergo 2 weeks of pre-treatment) prior to the first dose of chemotherapy and continued the application twice daily for the duration of the individual patient's chemotherapy (up to a maximum of 54 weeks).To determine the MTD for Compound 31543, dose escalation was conducted in stepwise increments, in the absence of dose-limiting toxicity (DLT) defined as clinically significant Grade 3 or 4 non-hematologic toxicity assessed as possibly, probably, or definitely related to Compound 31543 and not to the taxane-based chemotherapy, as best determined by investigator; assessment of DLTs was made weekly during the first 28 days of Compound 31543 treatment and subsequently thereafter every 4 weeks. Pharmacokinetic (PK) data were evaluated for each dose level before escalation of Compound 31543 to the next dose level in all patients. PK blood samples were collected on Day 1 prior (pre-dose) to the first-morning dose of topical Compound 31543 and at 2, 4, and 8 hours post-dose after the first application of Compound 31543 on Day 1. PK samples were also collected 12 hours after the last, evening dose of Compound 31543 (i.e., before the first Day 1 of the next 28-day treatment) on Weeks 5, 9, 13, and 54. Potential efficacy of the Compound 31543 was evaluated by photographic assessments and self-assessment diaries performed at baseline and Weeks 7, 15, 27, and 54. Photographic assessments were performed using a Canon digital camera system on views of the front of head/face, bilateral sides of head, and back and top of head/scalp view, as well as close-up photographs of a superior view and a vertex view with hair parted in the center and combed away from the part. Photographs were standardized for lighting, camera angle, and position to the participant's head. Additionally, patients maintained a medication application diary and a self-assessment diary. The patient completed diary collected patient-reported assessments of hair thickness, fullness, volume, breakage, and cosmetic qualities (ease of styling, etc.) based on a 10-point analog scale for each parameter/question during the first 15 weeks after initiating calcitriol Compound 31543 and at Weeks 19, 23, and 27.
Interventions
DRUGCompound 31543 Calcitriol 5 μg/mL
5 μg/mL Topical Solution
DRUGCompound 31543 Calcitriol 10 μg/mL
10 μg/mL Topical Solution
DRUGCompound 31543 Calcitriol 20 μg/mL
20 μg/mL Topical Solution
DRUGCompound 31543 Calcitriol 40 μg/mL
40 μg/mL Topical Solution
DRUGCompound 31543 Calcitriol 60 ug/mL
60 ug/mL Topical Solution
DRUGCompound 31543 Calcitriol 80 μg/mL
80 μg/mL Topical Solution
Sponsors
BPGbio
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
A standard 3+3 dose escalation design was employed, over 6 dose levels, with 3 to 6 patients at each dose level.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients at least 18 years of age * Able to fully understand and participate in the informed consent process * Patients who are scheduled to receive a taxane-based regimen for a histologically confirmed solid tumor that is: 1. Early stage and/or treatment naïve, or 2. Relapsed or is refractory to previous therapy, or 3. Operable and necessitates adjuvant or neo-adjuvant treatment * Have no evidence of alopecia or mild alopecia (NCI CTCAE v.4.0 grade 1 alopecia defined as hair loss of \<50% of normal for that individual that is not obvious from a distance but only on close inspection; a different hair style may be required to cover the hair loss but it does not require a wig or hair piece to camouflage). Female/male-pattern baldness or age-related hair loss are allowed if not greater than grade 1, per NCI-CTCAE v. 4.0. Patients that have previously lost their hair may enroll if they currently have Grade 0 or 1 alopecia * Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1 within 14 days prior to registration * Has baseline neutrophil counts of \> 1500 cells/mm3 within 72 hours prior to registration * Has serum calcium less than or equal to upper limit of normal (ULN) (for patients with an albumin lower than 3.0, a corrected calcium serum calcium = serum calcium +\[0.8\]\[3.5-serum albumin\]) within 72 hours prior to registration
Exclusion criteria
* Patients receiving calcium-lowering therapy or drugs that may affect calcium levels (e.g., calcitonin, mithramycin, phosphate, denosumab) within 4 weeks of initiation of topical calcitriol. Patients who have been managed with bisphosphonates or calcium-lowering therapy for 3 months or greater prior to the start of the trial and have demonstrated evidence for stability of calcium metabolism would be considered eligible for participation in the trial. * Has a history of drug or alcohol abuse within 1 year of study enrollment as determined by the investigator. * Patients who elect to shave the scalp hair prior to the initiation of chemotherapy or who plan to do so during the chemotherapy treatment. * Any dermatological condition that in the opinion of the investigator will affect the absorption of the study medication, e.g. Atopic Dermatitis, etc. * Has been treated with an investigational agent within 30 days or six half-lives of its biologic activity whichever is longer, before the start of study. (Patients may not be concurrently enrolled on another trial or concurrently treated with another investigational agent) * Patients with a history of hypercalcemia or vitamin D toxicity, or hospitalization for treatment of angina, myocardial infarction, or congestive heart failure or psychiatric illness currently or within 30 days of study entry as determined by the investigator. * Has a history of significant allergy to calcitriol as determined by the investigator. * Has any condition that interferes with the ability of the subject to understand or comply with the requirements of the study. * Patients taking Vitamin D supplements during the study, unless they have been taking Vitamin D supplements for 30 days or more prior to the start of the study and that the dose of the Vitamin D supplement remain the same throughout the study. * Patients treated with medications that are known to affect calcium levels within 4 weeks of initiation of topical therapy (\>500 IU vitamin A, calcium supplements, fluoride, antiepileptics).with the exception of patients on stable therapy for more than six months * Patients with hypercalcemia or kidney stones * Patients that indicate they have significant hair breakage or hair damage and associated hair loss from hair over-processing within the last 30 days due to peroxide applications, permanent hair coloring, bleaches, streaking, perms, relaxers and/or hair oxidative dyes. * Current alopecia grade 2 or greater as per NCI-CTCAE v.4.0, or significant hair loss or hair breakage * Prior radiation to the cranium * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting Toxicities (DLT) of Topical Compound 31543 | 28 days | DLTs were graded according to the CTCAE v4.0. A DLT was defined as a clinically significant Grade 3 or 4 (severe or life-threatening, respectively) non-hematologic toxicity occurring during the first 28-day treatment cycle, and determined to be possibly, probably, or definitely related to BPM31543 and not the taxane-based regimen as best determined by investigators. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Week 1 Day 1 Concentrations of Compound 31543 | At 0, 2, 4, and 8 h on Week 1 Day 1 | Concentrations of Compound 31543 from serum samples collected on Week 1 Day 1 pre-dose and at 2 ± 0.5 hours, 4 ± 0.5 hours, and 8 ± 1 hours post-dose. |
| Cmax of Compound 31543 on Week 1 Day 1 | 8 hours | Cmax of Compound 31543 was calculated using serum samples collected on Week 1 Day 1 pre-dose and at 2 ± 0.5 hours, 4 ± 0.5 hours, and 8 ± 1 hours post-dose. The 8-hour Week 1 Day 1 sample was collected before the second of the daily doses. |
| AUC0-t of Compound 31543 on Week 1 Day 1 | 8 hours | Area under the curve (AUC0-t) of Compound 31543 was calculated from serum samples collected on Week 1 Day 1 pre-dose and at 2 ± 0.5 hours, 4 ± 0.5 hours, and 8 ± 1 hours post-dose. The 8-hour Week 1 Day 1 sample was collected before the second of the daily doses. |
| Pre-Dose Concentrations of Compound 31543 at Week 5 | Pre-dose Week 5 | Concentrations of Compound 31543 from serum samples collected pre-dose on Week 5 and \>10 hours post previous dose. |
| Pre-Dose Concentrations of Compound 31543 at Week 9 | Pre-dose Week 9 | Concentrations of Compound 31543 from serum samples collected pre-dose on Week 9 and \>10 hours post previous dose. |
| Pre-Dose Concentrations of Compound 31543 at Week 13 | Pre-dose Week 13 | Concentrations of Compound 31543 from serum samples collected pre-dose on Week 13 and \>10 hours post previous dose. |
| Top View Photographic Review Score | 7 and 15 weeks | Top of head/scalp view at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain. |
| Right Side Photographic Review Score | 7 and 15 weeks | Right side of head/scalp view at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain. |
| Left Side Photographic Review Score | 7 and 15 weeks | Left side of head/scalp view at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain. |
| Front Photographic Review Score | 7 and 15 weeks | Front of head/face view at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain. |
| Back Photographic Review Score | 7 and 15 weeks | Back of head/face view at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain. |
| Superior (Mid Pattern) Photographic Review Score | 7 and 15 weeks | Mid-pattern of the scalp from a superior view at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain. |
| Vertex Photographic Review Score | 7 and 15 weeks | Vertex view with hair parted in the center at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMario E Lacouture, MD
Memorial Sloan Kettering Cancer Center
PRINCIPAL_INVESTIGATORShari Goldfarb, MD
Memorial Sloan Kettering Cancer Center
PRINCIPAL_INVESTIGATORMonica Mita, MD
Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai
Participant flow
Recruitment details
Conducted at 2 US sites
Pre-assignment details
Patients scheduled to receive follow up treatment with a taxane-based chemotherapy regimen
Participants by arm
| Arm | Count |
|---|---|
| Compound 31543 Calcitriol - 5 ug/mL Compound 31543 Calcitriol (5 ug/mL), Topical application, 0.25 mL to be applied to each of the four quadrants of the scalp twice daily, morning and night with 10-14 hours between applications either for 2 weeks or 7 ± 2 days (if the patient was unable or unwilling to undergo 2 weeks of pre-treatment) prior to the first dose of chemotherapy and continued the application twice daily for the duration of the individual patient's chemotherapy (up to a maximum of 54 weeks). | 3 |
| Compound 31543 Calcitriol - 10 ug/mL Compound 31543 Calcitriol (10 ug/mL), Topical application, 0.25 mL to be applied to each of the four quadrants of the scalp twice daily, morning and night with 10-14 hours between applications either for 2 weeks or 7 ± 2 days (if the patient was unable or unwilling to undergo 2 weeks of pre-treatment) prior to the first dose of chemotherapy and continued the application twice daily for the duration of the individual patient's chemotherapy (up to a maximum of 54 weeks). | 3 |
| Compound 31543 Calcitriol - 20 ug/mL Compound 31543 Calcitriol (20 ug/mL), Topical application, 0.25 mL to be applied to each of the four quadrants of the scalp twice daily, morning and night with 10-14 hours between applications either for 2 weeks or 7 ± 2 days (if the patient was unable or unwilling to undergo 2 weeks of pre-treatment) prior to the first dose of chemotherapy and continued the application twice daily for the duration of the individual patient's chemotherapy (up to a maximum of 54 weeks). | 6 |
| Compound 31543 Calcitriol - 40 ug/mL Compound 31543 Calcitriol (40 ug/mL), Topical application, 0.25 mL to be applied to each of the four quadrants of the scalp twice daily, morning and night with 10-14 hours between applications either for 2 weeks or 7 ± 2 days (if the patient was unable or unwilling to undergo 2 weeks of pre-treatment) prior to the first dose of chemotherapy and continued the application twice daily for the duration of the individual patient's chemotherapy (up to a maximum of 54 weeks). | 4 |
| Compound 31543 Calcitriol - 60 ug/mL Compound 31543 Calcitriol (60 ug/mL), Topical application, 0.25 mL to be applied to each of the four quadrants of the scalp twice daily, morning and night with 10-14 hours between applications either for 2 weeks or 7 ± 2 days (if the patient was unable or unwilling to undergo 2 weeks of pre-treatment) prior to the first dose of chemotherapy and continued the application twice daily for the duration of the individual patient's chemotherapy (up to a maximum of 54 weeks). | 4 |
| Compound 31543 Calcitriol - 80 ug/mL Compound 31543 Calcitriol (80 ug/mL), Topical application, 0.25 mL to be applied to each of the four quadrants of the scalp twice daily, morning and night with 10-14 hours between applications either for 2 weeks or 7 ± 2 days (if the patient was unable or unwilling to undergo 2 weeks of pre-treatment) prior to the first dose of chemotherapy and continued the application twice daily for the duration of the individual patient's chemotherapy (up to a maximum of 54 weeks). | 3 |
| Total | 23 |
Baseline characteristics
| Characteristic | Compound 31543 Calcitriol - 5 ug/mL | Compound 31543 Calcitriol - 10 ug/mL | Compound 31543 Calcitriol - 20 ug/mL | Compound 31543 Calcitriol - 40 ug/mL | Compound 31543 Calcitriol - 60 ug/mL | Compound 31543 Calcitriol - 80 ug/mL | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.7 years STANDARD_DEVIATION 8.5 | 47.0 years STANDARD_DEVIATION 6.08 | 54.0 years STANDARD_DEVIATION 12.98 | 51.0 years STANDARD_DEVIATION 17.83 | 47.3 years STANDARD_DEVIATION 18.46 | 58.0 years STANDARD_DEVIATION 12.17 | 51.7 years STANDARD_DEVIATION 12.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 6 Participants | 3 Participants | 3 Participants | 2 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants | 19 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants | 4 Participants | 4 Participants | 3 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 | 4 / 4 | 3 / 4 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 1 / 3 | 1 / 6 | 4 / 4 | 1 / 4 | 2 / 3 |
Outcome results
Primary
Dose-limiting Toxicities (DLT) of Topical Compound 31543
DLTs were graded according to the CTCAE v4.0. A DLT was defined as a clinically significant Grade 3 or 4 (severe or life-threatening, respectively) non-hematologic toxicity occurring during the first 28-day treatment cycle, and determined to be possibly, probably, or definitely related to BPM31543 and not the taxane-based regimen as best determined by investigators.
Time frame: 28 days
Population: Consisted of all patients who received at least one application of Compound 31543.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Compound 31543 Calcitriol - 5 μg/mL | Dose-limiting Toxicities (DLT) of Topical Compound 31543 | 0 Participants |
| Compound 31543 Calcitriol - 10 μg/mL | Dose-limiting Toxicities (DLT) of Topical Compound 31543 | 0 Participants |
| Compound 31543 Calcitriol - 20 μg/mL | Dose-limiting Toxicities (DLT) of Topical Compound 31543 | 0 Participants |
| Compound 31543 Calcitriol - 40 μg/mL | Dose-limiting Toxicities (DLT) of Topical Compound 31543 | 0 Participants |
| Compound 31543 Calcitriol - 60 μg/mL | Dose-limiting Toxicities (DLT) of Topical Compound 31543 | 0 Participants |
| Compound 31543 Calcitriol - 80 μg/mL | Dose-limiting Toxicities (DLT) of Topical Compound 31543 | 0 Participants |
Secondary
AUC0-t of Compound 31543 on Week 1 Day 1
Area under the curve (AUC0-t) of Compound 31543 was calculated from serum samples collected on Week 1 Day 1 pre-dose and at 2 ± 0.5 hours, 4 ± 0.5 hours, and 8 ± 1 hours post-dose. The 8-hour Week 1 Day 1 sample was collected before the second of the daily doses.
Time frame: 8 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Compound 31543 Calcitriol - 5 μg/mL | AUC0-t of Compound 31543 on Week 1 Day 1 | 346 pg•hour/mL | Standard Deviation 10 |
| Compound 31543 Calcitriol - 10 μg/mL | AUC0-t of Compound 31543 on Week 1 Day 1 | 334 pg•hour/mL | Standard Deviation 163 |
| Compound 31543 Calcitriol - 20 μg/mL | AUC0-t of Compound 31543 on Week 1 Day 1 | 259 pg•hour/mL | Standard Deviation 60 |
| Compound 31543 Calcitriol - 40 μg/mL | AUC0-t of Compound 31543 on Week 1 Day 1 | 530 pg•hour/mL | Standard Deviation 165 |
| Compound 31543 Calcitriol - 60 μg/mL | AUC0-t of Compound 31543 on Week 1 Day 1 | 230 pg•hour/mL | Standard Deviation 87 |
| Compound 31543 Calcitriol - 80 μg/mL | AUC0-t of Compound 31543 on Week 1 Day 1 | 370 pg•hour/mL | Standard Deviation 99 |
Secondary
Back Photographic Review Score
Back of head/face view at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain.
Time frame: 7 and 15 weeks
Population: Evaluable Population defined as all patients who completed at least one photographic assessment and diary completion through Week 7. Some patients discontinued treatment prior to week 15 and are therefore only analyzed at week 7.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Compound 31543 Calcitriol - 5 μg/mL | Back Photographic Review Score | Week 15 | -2 score on a scale | — |
| Compound 31543 Calcitriol - 5 μg/mL | Back Photographic Review Score | Week 7 | -0.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 10 μg/mL | Back Photographic Review Score | Week 7 | -0.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 20 μg/mL | Back Photographic Review Score | Week 15 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 20 μg/mL | Back Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 40 μg/mL | Back Photographic Review Score | Week 15 | -3 score on a scale | — |
| Compound 31543 Calcitriol - 40 μg/mL | Back Photographic Review Score | Week 7 | -2 score on a scale | Standard Deviation 1 |
| Compound 31543 Calcitriol - 60 μg/mL | Back Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 60 μg/mL | Back Photographic Review Score | Week 15 | -2 score on a scale | Standard Deviation 1.41 |
| Compound 31543 Calcitriol - 80 μg/mL | Back Photographic Review Score | Week 15 | -2.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 80 μg/mL | Back Photographic Review Score | Week 7 | -2 score on a scale | Standard Deviation 1 |
Secondary
Cmax of Compound 31543 on Week 1 Day 1
Cmax of Compound 31543 was calculated using serum samples collected on Week 1 Day 1 pre-dose and at 2 ± 0.5 hours, 4 ± 0.5 hours, and 8 ± 1 hours post-dose. The 8-hour Week 1 Day 1 sample was collected before the second of the daily doses.
Time frame: 8 hours
Population: Pharmacokinetic Parameters for Serum Calcitriol Concentrations on Week 1, Day 1 of BPM31543 Administration (PK Population)~The pharmacokinetic evaluable population was intended to include all patients with concentration results for the four samples scheduled for Week 1 Day 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Compound 31543 Calcitriol - 5 μg/mL | Cmax of Compound 31543 on Week 1 Day 1 | 51.6 pg/mL | Standard Deviation 6.9 |
| Compound 31543 Calcitriol - 10 μg/mL | Cmax of Compound 31543 on Week 1 Day 1 | 47.2 pg/mL | Standard Deviation 13.6 |
| Compound 31543 Calcitriol - 20 μg/mL | Cmax of Compound 31543 on Week 1 Day 1 | 42.5 pg/mL | Standard Deviation 8.5 |
| Compound 31543 Calcitriol - 40 μg/mL | Cmax of Compound 31543 on Week 1 Day 1 | 81.0 pg/mL | Standard Deviation 8.1 |
| Compound 31543 Calcitriol - 60 μg/mL | Cmax of Compound 31543 on Week 1 Day 1 | 36.0 pg/mL | Standard Deviation 9.8 |
| Compound 31543 Calcitriol - 80 μg/mL | Cmax of Compound 31543 on Week 1 Day 1 | 53.5 pg/mL | Standard Deviation 16.1 |
Secondary
Front Photographic Review Score
Front of head/face view at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain.
Time frame: 7 and 15 weeks
Population: Evaluable Population defined as all patients who completed at least one photographic assessment and diary completion through Week 7. Some patients discontinued treatment prior to week 15 and are therefore only analyzed at week 7.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Compound 31543 Calcitriol - 5 μg/mL | Front Photographic Review Score | Week 15 | -2 score on a scale | — |
| Compound 31543 Calcitriol - 5 μg/mL | Front Photographic Review Score | Week 7 | -0.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 10 μg/mL | Front Photographic Review Score | Week 7 | -0.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 20 μg/mL | Front Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 20 μg/mL | Front Photographic Review Score | Week 15 | -1.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 40 μg/mL | Front Photographic Review Score | Week 7 | -1.7 score on a scale | Standard Deviation 0.58 |
| Compound 31543 Calcitriol - 40 μg/mL | Front Photographic Review Score | Week 15 | -2 score on a scale | — |
| Compound 31543 Calcitriol - 60 μg/mL | Front Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 60 μg/mL | Front Photographic Review Score | Week 15 | -2 score on a scale | Standard Deviation 1.41 |
| Compound 31543 Calcitriol - 80 μg/mL | Front Photographic Review Score | Week 15 | -2.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 80 μg/mL | Front Photographic Review Score | Week 7 | -2.3 score on a scale | Standard Deviation 0.58 |
Secondary
Left Side Photographic Review Score
Left side of head/scalp view at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain.
Time frame: 7 and 15 weeks
Population: Evaluable Population defined as all patients who completed at least one photographic assessment and diary completion through Week 7. Some patients discontinued treatment prior to week 15 and are therefore only analyzed at week 7.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Compound 31543 Calcitriol - 5 μg/mL | Left Side Photographic Review Score | Week 15 | -2 score on a scale | — |
| Compound 31543 Calcitriol - 5 μg/mL | Left Side Photographic Review Score | Week 7 | -0.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 10 μg/mL | Left Side Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 20 μg/mL | Left Side Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 20 μg/mL | Left Side Photographic Review Score | Week 15 | -1.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 40 μg/mL | Left Side Photographic Review Score | Week 7 | -2.3 score on a scale | Standard Deviation 1.15 |
| Compound 31543 Calcitriol - 40 μg/mL | Left Side Photographic Review Score | Week 15 | -3 score on a scale | — |
| Compound 31543 Calcitriol - 60 μg/mL | Left Side Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 60 μg/mL | Left Side Photographic Review Score | Week 15 | -2 score on a scale | Standard Deviation 1.41 |
| Compound 31543 Calcitriol - 80 μg/mL | Left Side Photographic Review Score | Week 15 | -2.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 80 μg/mL | Left Side Photographic Review Score | Week 7 | -1.7 score on a scale | Standard Deviation 0.58 |
Secondary
Pre-dose Concentrations of Compound 31543
Pre-dose concentrations of Compound 31543 from serum samples collected on Week 1 Day 1.
Time frame: pre-dose on day 1 of Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Compound 31543 Calcitriol - 5 μg/mL | Pre-dose Concentrations of Compound 31543 | 49.0 pg/mL | Standard Deviation 5.8 |
| Compound 31543 Calcitriol - 10 μg/mL | Pre-dose Concentrations of Compound 31543 | 43.2 pg/mL | Standard Deviation 14.8 |
| Compound 31543 Calcitriol - 20 μg/mL | Pre-dose Concentrations of Compound 31543 | 54.3 pg/mL | Standard Deviation 31.5 |
| Compound 31543 Calcitriol - 40 μg/mL | Pre-dose Concentrations of Compound 31543 | 58.4 pg/mL | Standard Deviation 19.4 |
| Compound 31543 Calcitriol - 60 μg/mL | Pre-dose Concentrations of Compound 31543 | 32.8 pg/mL | Standard Deviation 5.2 |
| Compound 31543 Calcitriol - 80 μg/mL | Pre-dose Concentrations of Compound 31543 | 37.8 pg/mL | Standard Deviation 15.5 |
Secondary
Right Side Photographic Review Score
Right side of head/scalp view at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain.
Time frame: 7 and 15 weeks
Population: Evaluable Population defined as all patients who completed at least one photographic assessment and diary completion through Week 7. Some patients discontinued treatment prior to week 15 and are therefore only analyzed at week 7.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Compound 31543 Calcitriol - 5 μg/mL | Right Side Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 5 μg/mL | Right Side Photographic Review Score | Week 15 | -2 score on a scale | — |
| Compound 31543 Calcitriol - 10 μg/mL | Right Side Photographic Review Score | Week 7 | -2 score on a scale | — |
| Compound 31543 Calcitriol - 20 μg/mL | Right Side Photographic Review Score | Week 15 | -1.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 20 μg/mL | Right Side Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 40 μg/mL | Right Side Photographic Review Score | Week 7 | -2.3 score on a scale | Standard Deviation 1.15 |
| Compound 31543 Calcitriol - 40 μg/mL | Right Side Photographic Review Score | Week 15 | -3 score on a scale | — |
| Compound 31543 Calcitriol - 60 μg/mL | Right Side Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 60 μg/mL | Right Side Photographic Review Score | Week 15 | -2 score on a scale | Standard Deviation 1.41 |
| Compound 31543 Calcitriol - 80 μg/mL | Right Side Photographic Review Score | Week 15 | -2.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 80 μg/mL | Right Side Photographic Review Score | Week 7 | -1.7 score on a scale | Standard Deviation 0.58 |
Secondary
Superior (Mid Pattern) Photographic Review Score
Mid-pattern of the scalp from a superior view at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain.
Time frame: 7 and 15 weeks
Population: Evaluable Population defined as all patients who completed at least one photographic assessment and diary completion through Week 7. Some patients discontinued treatment prior to week 15 and are therefore only analyzed at week 7.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Compound 31543 Calcitriol - 5 μg/mL | Superior (Mid Pattern) Photographic Review Score | Week 7 | -1 score on a scale | — |
| Compound 31543 Calcitriol - 10 μg/mL | Superior (Mid Pattern) Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 20 μg/mL | Superior (Mid Pattern) Photographic Review Score | Week 15 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 20 μg/mL | Superior (Mid Pattern) Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 40 μg/mL | Superior (Mid Pattern) Photographic Review Score | Week 15 | -2 score on a scale | — |
| Compound 31543 Calcitriol - 40 μg/mL | Superior (Mid Pattern) Photographic Review Score | Week 7 | -1.7 score on a scale | Standard Deviation 0.58 |
| Compound 31543 Calcitriol - 60 μg/mL | Superior (Mid Pattern) Photographic Review Score | Week 7 | -0.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 60 μg/mL | Superior (Mid Pattern) Photographic Review Score | Week 15 | -2 score on a scale | Standard Deviation 1.41 |
| Compound 31543 Calcitriol - 80 μg/mL | Superior (Mid Pattern) Photographic Review Score | Week 15 | -2.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 80 μg/mL | Superior (Mid Pattern) Photographic Review Score | Week 7 | -1.7 score on a scale | Standard Deviation 0.58 |
Secondary
Top View Photographic Review Score
Top of head/scalp view at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain.
Time frame: 7 and 15 weeks
Population: Evaluable Population defined as all patients who completed at least one photographic assessment and diary completion through Week 7. Some patients discontinued treatment prior to week 15 and are therefore only analyzed at week 7.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Compound 31543 Calcitriol - 5 μg/mL | Top View Photographic Review Score | Week 15 | -2 score on a scale | — |
| Compound 31543 Calcitriol - 5 μg/mL | Top View Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 10 μg/mL | Top View Photographic Review Score | Week 7 | -1.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 20 μg/mL | Top View Photographic Review Score | Week 7 | -1 score on a scale | — |
| Compound 31543 Calcitriol - 20 μg/mL | Top View Photographic Review Score | Week 15 | -1 score on a scale | — |
| Compound 31543 Calcitriol - 40 μg/mL | Top View Photographic Review Score | Week 7 | -3 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 40 μg/mL | Top View Photographic Review Score | Week 15 | -3 score on a scale | — |
| Compound 31543 Calcitriol - 60 μg/mL | Top View Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 60 μg/mL | Top View Photographic Review Score | Week 15 | -2 score on a scale | Standard Deviation 1.41 |
| Compound 31543 Calcitriol - 80 μg/mL | Top View Photographic Review Score | Week 15 | -3 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 80 μg/mL | Top View Photographic Review Score | Week 7 | -2 score on a scale | Standard Deviation 1 |
Secondary
Vertex Photographic Review Score
Vertex view with hair parted in the center at 7 and 15 weeks were compared to baseline images and scored on a 7-point evaluation scale: -3 = \>75% great hair loss; -2 = 50-75% moderate hair loss; -1 = 25-49% slight hair loss; 0 = 0-24% hair loss/gain, 1 = 25-49% slight hair gain; 2 = 50-75% moderate hair gain; 3 = \>75% greatly increased/hair gain.
Time frame: 7 and 15 weeks
Population: Evaluable Population defined as all patients who completed at least one photographic assessment and diary completion through Week 7. Not all patients had this photograph taken. Some patients discontinued treatment prior to week 15 and are therefore only analyzed at week 7.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Compound 31543 Calcitriol - 20 μg/mL | Vertex Photographic Review Score | Week 15 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 20 μg/mL | Vertex Photographic Review Score | Week 7 | -1 score on a scale | Standard Deviation 0 |
| Compound 31543 Calcitriol - 40 μg/mL | Vertex Photographic Review Score | Week 15 | -2 score on a scale | — |
| Compound 31543 Calcitriol - 40 μg/mL | Vertex Photographic Review Score | Week 7 | -1.7 score on a scale | Standard Deviation 0.58 |
| Compound 31543 Calcitriol - 60 μg/mL | Vertex Photographic Review Score | Week 7 | -0.5 score on a scale | Standard Deviation 0.71 |
| Compound 31543 Calcitriol - 60 μg/mL | Vertex Photographic Review Score | Week 15 | -1.5 score on a scale | Standard Deviation 2.12 |
| Compound 31543 Calcitriol - 80 μg/mL | Vertex Photographic Review Score | Week 7 | -1.7 score on a scale | Standard Deviation 0.58 |
| Compound 31543 Calcitriol - 80 μg/mL | Vertex Photographic Review Score | Week 15 | -2.5 score on a scale | Standard Deviation 0.71 |