Trial Outcomes & Findings for A Maximal Use Trial Evaluating the Pharmacokinetic Profile of MC2-01 Cream (NCT NCT03462927)

NCT ID: NCT03462927

Last Updated: 2019-12-24

Results Overview

Geometric Mean for Maximum Plasma Concentration \[Cmax\] for the active ingredient Calcipotriene. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 63 participants
• Primary outcome timeframe: Week 4
• Results posted on: 2019-12-24

Participant Flow

First Subject First Visit: 08Feb-2018. Last Subject Last Visit: 04-Aug-2018.

Prior to randomization, the subject entered a washout period (if required) where anti-psoriatic treatment and other relevant medication/treatments were discontinued as defined by the exclusion criteria. The washout/screening period lasted for up to 4 weeks depending on which disallowed treatments the subject received.

Participant milestones

Measure	MC2-01 Cream MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/ 0.064%). One application daily for 8 weeks. MC2-01 Cream: MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%)	CAL/BDP Combination CAL/BDP ointment (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%, w/w 0.005%/0.064%). One daily application for 4 weeks. CAL/BDP combination: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Overall Study STARTED	32	31
Overall Study COMPLETED	26	29
Overall Study NOT COMPLETED	6	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Maximal Use Trial Evaluating the Pharmacokinetic Profile of MC2-01 Cream

Baseline characteristics by cohort

Measure	MC2-01 Cream n=32 Participants MC2-01 cream (CAL and BDP, w/w 0.005%/ 0.064%). MC2-01 Cream: MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%)	CAL/BDP Combination n=31 Participants CAL/BDP ointment (w/w 0.005%/0.064%). CAL/BDP combination: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)	Total n=63 Participants Total of all reporting groups
Age, Continuous	52.8 years STANDARD_DEVIATION 15.5 • n=5 Participants	49.7 years STANDARD_DEVIATION 16.2 • n=7 Participants	51.3 years STANDARD_DEVIATION 15.8 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	21 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	28 Participants n=7 Participants	56 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	32 participants n=5 Participants	31 participants n=7 Participants	63 participants n=5 Participants
Baseline Physician's Global Assessment (PGA) Moderate	29 Participants n=5 Participants	30 Participants n=7 Participants	59 Participants n=5 Participants
Baseline Physician's Global Assessment (PGA) Severe	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Baseline Body Surface Area (BSA)	23.56 Percentage of psoriasis involvement STANDARD_DEVIATION 2.52 • n=5 Participants	24.09 Percentage of psoriasis involvement STANDARD_DEVIATION 3.13 • n=7 Participants	23.82 Percentage of psoriasis involvement STANDARD_DEVIATION 2.82 • n=5 Participants
Fitzpatrick Skin Type I	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Fitzpatrick Skin Type II	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Fitzpatrick Skin Type III	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Fitzpatrick Skin Type IV	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Fitzpatrick Skin Type V	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Fitzpatrick Skin Type VI	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 4

Population: 9 subjects were excluded from the PK evaluation at Week 4: 5 in the MC2-01 cream group and 4 in the active comparator group

Geometric Mean for Maximum Plasma Concentration [Cmax] for the active ingredient Calcipotriene. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose

Outcome measures

Measure	MC2-01 Cream n=27 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment n=27 Participants CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Maximum Plasma Concentration (Cmax) of the Active Ingredient Calcipotriene	30.2 pg/mL Interval 29.8 to 30.7	30.0 pg/mL Interval 30.0 to 30.0

PRIMARY outcome

Timeframe: Week 8

Population: As per protocol, only subjects assigned to the MC2-01 cream had samples for PK testing collected at week 8. Only subjects that had a computable value of the PK parameter have been included in the analysis

Geometric Mean for Maximum Plasma Concentration [Cmax] for the active ingredient Calcipotriene. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose

Outcome measures

Measure	MC2-01 Cream n=19 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Maximum Plasma Concentration (Cmax) of the Active Ingredient Calcipotriene	30.0 pg/mL Interval 30.0 to 30.0	—

PRIMARY outcome

Timeframe: Week 4

Population: 9 subjects were excluded from the PK evaluation at Week 4: 5 in the MC2-01 cream group and 4 in the active comparator group

Geometric Mean for Maximum Plasma Concentration [Cmax] for the active ingredient Betamethasone Dipropionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose

Outcome measures

Measure	MC2-01 Cream n=27 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment n=27 Participants CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Maximum Plasma Concentration (Cmax) of Active Ingredient Betamethasone Dipropionate	21.5 pg/mL Interval 19.5 to 23.7	23.1 pg/mL Interval 19.0 to 28.1

PRIMARY outcome

Timeframe: Week 8

Population: As per protocol, only subjects assigned to the MC2-01 cream had samples for PK testing collected at week 8. Only subjects that had a computable value of the PK parameter have been included in the analysis

Geometric Mean for Maximum Plasma Concentration [Cmax] for the active ingredient Betamethasone Dipropionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose

Outcome measures

Measure	MC2-01 Cream n=19 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Maximum Plasma Concentration (Cmax) of Active Ingredient Betamethasone Dipropionate	20.0 pg/mL Interval 20.0 to 20.0	—

PRIMARY outcome

Timeframe: Week 4

Population: 9 subjects were excluded from the PK evaluation at Week 4: 5 in the MC2-01 cream group and 4 in active comparator group

Geometric Mean for Maximum Plasma Concentration [Cmax] for the metabolite MC1080. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose

Outcome measures

Measure	MC2-01 Cream n=27 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment n=27 Participants CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Maximum Plasma Concentration (Cmax) of the Metabolite MC1080	29.8 pg/mL Interval 28.7 to 31.0	29.2 pg/mL Interval 29.0 to 29.3

PRIMARY outcome

Timeframe: Week 8

Population: As per protocol, only subjects assigned to the MC2-01 cream had samples for PK testing collected at week 8. Only subjects that had a computable value of the PK parameter have been included in the analysis

Geometric Mean for Maximum Plasma Concentration [Cmax] for the metabolite MC1080. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose

Outcome measures

Measure	MC2-01 Cream n=19 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Maximum Plasma Concentration (Cmax) of the Metabolite MC1080	29.1 pg/mL Interval 29.1 to 29.1	—

PRIMARY outcome

Timeframe: Week 4

Population: 9 subjects were excluded from the PK evaluation at Week 4: 5 in the MC2-01 cream group and 4 in active comparator group

Geometric Mean for Maximum Plasma Concentration [Cmax] for the metabolite Betamethasone 17-propionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose

Outcome measures

Measure	MC2-01 Cream n=27 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment n=27 Participants CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Maximum Plasma Concentration (Cmax) of Metabolite Betamethasone 17-propionate	39.3 pg/mL Interval 25.8 to 59.8	38.2 pg/mL Interval 27.4 to 53.4

PRIMARY outcome

Timeframe: Week 8

Population: As per protocol, only subjects assigned to the MC2-01 cream had samples for PK testing collected at week 8. Only subjects that had a computable value of the PK parameter have been included in the analysis

Geometric Mean for Maximum Plasma Concentration [Cmax] for the metabolite Betamethasone 17-propionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose

Outcome measures

Measure	MC2-01 Cream n=19 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Maximum Plasma Concentration (Cmax) of Metabolite Betamethasone 17-propionate	26.2 pg/mL Interval 20.5 to 33.5	—

SECONDARY outcome

Timeframe: Week 4

Population: The HPA challenge test were only performed on subjects that were assigned to the MC2-01 cream group. No data were collected from the CAL/BDP Ointment group. Out of a total of 32 subjects, 5 subjects were excluded from the analysis as they had HPA suppression at baseline

The HPA axis evaluation is based on an Adrenocorticotropic hormone [ACTH] challenge test, defined by a 30 minutes ACTH stimulated cortisol value. Only subject with no HPA suppression at baseline were included in the analysis.

The outcome measure lists the number of subjects with HPA suppression 30 minutes after ACTH challenge

Outcome measures

Measure	MC2-01 Cream n=27 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Number of Subjects With Hypothalamic-pituitary-adrenal [HPA] Suppression After 4 Weeks of Treatment	1 Participants	—

SECONDARY outcome

Timeframe: Week 8

Population: The HPA challenge test were only performed on subjects that were assigned to the MC2-01 cream group. No data were collected from the CAL/BDP Ointment group. Out of a total of 32 subjects, 6 subjects were excluded from the analysis; 5 as they had HPA suppression at baseline and 1 who withdrew consent

The HPA challenge test were only performed on subjects that were assigned to the MC2-01 cream group. Out of a total of 32 subjects, 5 subjects were excluded from the analysis as they had HPA suppression at baseline

Outcome measures

Measure	MC2-01 Cream n=26 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Number of Subjects With Hypothalamic-pituitary-adrenal [HPA] Suppression After 8 Weeks of Treatment	2 Participants	—

SECONDARY outcome

Timeframe: Baseline and week 4

Population: As per protocol, only subjects assigned to the MC2-01 cream were included in the calcium metabolism evaluation. No data were collected from the CAL/BDP Ointment group. 5 subjects in the MC2-01 cream group were excluded from the analysis

Changes from baseline of albumin-corrected serum calcium [mmol/L]

Outcome measures

Measure	MC2-01 Cream n=27 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Calcium Metabolism Evaluation in Albumin-corrected Serum Calcium	-0.00 mmol/L Standard Deviation 0.09	—

SECONDARY outcome

Timeframe: Baseline and week 8

Population: As per protocol, only subjects assigned to the MC2-01 cream were included in the calcium metabolism evaluation. No data were collected from the CAL/BDP Ointment group. 6 subjects in the MC2-01 cream group were excluded from the analysis

Changes from baseline in albumin-corrected serum calcium [mmol/L]

Outcome measures

Measure	MC2-01 Cream n=26 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Calcium Metabolism Evaluation in Albumin-corrected Serum Calcium	0.00 mmol/L Standard Deviation 0.07	—

SECONDARY outcome

Timeframe: Baseline and week 4

Population: As per protocol, only subjects assigned to the MC2-01 cream were included in the calcium metabolism evaluation. No data were collected from the CAL/BDP Ointment group. 8 subjects in the MC2-01 cream group were excluded from the analysis

Changes from baseline of 24-hour urinary calcium excretion [mmol/day]

Outcome measures

Measure	MC2-01 Cream n=24 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Calcium Metabolism Evaluation of 24-hour Urinary Calcium Excretion	-0.56 mmol/day Standard Deviation 1.69	—

SECONDARY outcome

Timeframe: Baseline and week 8

Population: As per protocol, only subjects assigned to the MC2-01 cream were included in the calcium metabolism evaluation. No data were collected from the CAL/BDP Ointment group. 12 subjects in the MC2-01 cream group were excluded from the analysis

Changes from baseline of 24-hour urinary calcium excretion [mmol/day]

Outcome measures

Measure	MC2-01 Cream n=20 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Calcium Metabolism Evaluation of 24-hour Urinary Calcium Excretion	-0.45 mmol/day Standard Deviation 1.08	—

SECONDARY outcome

Timeframe: Baseline and week 4

Population: As per protocol, only subjects assigned to the MC2-01 cream were included in the calcium metabolism evaluation. No data were collected from the CAL/BDP Ointment group. 8 subjects in the MC2-01 cream group were excluded from the analysis

Changes from baseline in ratio of urinary calcium to creatinine defined as urinary calcium (mmol)/creatinine (g)

Outcome measures

Measure	MC2-01 Cream n=24 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Calcium Metabolism Evaluation of the Ratio of Urinary Calcium to Creatinine	-0.23 mmol/g Standard Deviation 1.49	—

SECONDARY outcome

Timeframe: Baseline and week 8

Population: As per protocol, only subjects assigned to the MC2-01 cream were included in the calcium metabolism evaluation. No data were collected from the CAL/BDP Ointment group. 12 subjects in the MC2-01 cream group were excluded from the analysis

Changes from baseline in ratio of urinary calcium to creatinine defined as urinary calcium (mmol)/creatinine (g)

Outcome measures

Measure	MC2-01 Cream n=20 Participants MC2-01 cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%).	CAL/BDP Ointment CAL/BDP ointment: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Calcium Metabolism Evaluation of the Ratio of Urinary Calcium to Creatinine	0.00 mmol/g Standard Deviation 1.32	—

Adverse Events

MC2-01 Cream

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

CAL/BDP Combination

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	MC2-01 Cream n=32 participants at risk MC2-01 cream (CAL and BDP, w/w 0.005%/ 0.064%). MC2-01 Cream: MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%)	CAL/BDP Combination n=31 participants at risk CAL/BDP ointment (w/w 0.005%/0.064%). CAL/BDP combination: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)
Musculoskeletal and connective tissue disorders Ankle Fracture	0.00% 0/32 • AEs were collected/assessed from the time of the signature of the informed consent form by the subject during the screening visit (up to 4 weeks prior to treatment), during the treatment period (up to 8 weeks) and until the final follow-up visit had occurred (up to 4 weeks following end of treatment). All AEs that were considered related to the trial product would be followed until they were resolved, or until the medical condition of the subject was stable	3.2% 1/31 • Number of events 1 • AEs were collected/assessed from the time of the signature of the informed consent form by the subject during the screening visit (up to 4 weeks prior to treatment), during the treatment period (up to 8 weeks) and until the final follow-up visit had occurred (up to 4 weeks following end of treatment). All AEs that were considered related to the trial product would be followed until they were resolved, or until the medical condition of the subject was stable

Other adverse events

Adverse event data not reported

Additional Information

Birgitte Vestbjerg

MC2 Therapeutics

Phone: +45 2077 2575

Email: bve@mc2therapeutics.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60