Trial Outcomes & Findings for Pharmacokinetic Interaction Between SSP-004184 (SPD602) and Midazolam in Healthy Adult Subjects (NCT NCT01989169)

Results Overview

AUCinf is the area under the plasma concentration versus time curve extrapolated from time 0 to infinity, calculated using the observed value of the last non-zero concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

Study Periods 1 & 2: Within 60 minutes pre-dose, and Post-dose 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72 hours.

Results posted on

2021-06-24

Participant Flow

Participant milestones

Participant milestones
Measure	Midazolam First Subjects received Midazolam 6mg in Period 1, followed by Midazolam 6mg and SSP-004184SS 30mg/kg during Period 2.	Midazolam + SSP-004184SS First Subjects received Midazolam 6mg and SSP-004184SS 30mg/kg in Period 1, followed by Midazolam 6mg during Period 2.
Period 1 STARTED	15	15
Period 1 COMPLETED	15	15
Period 1 NOT COMPLETED	0	0
Period 2 STARTED	15	15
Period 2 COMPLETED	15	14
Period 2 NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Midazolam First Subjects received Midazolam 6mg in Period 1, followed by Midazolam 6mg and SSP-004184SS 30mg/kg during Period 2.	Midazolam + SSP-004184SS First Subjects received Midazolam 6mg and SSP-004184SS 30mg/kg in Period 1, followed by Midazolam 6mg during Period 2.
Period 2 Adverse Event	0	1

Baseline Characteristics

Pharmacokinetic Interaction Between SSP-004184 (SPD602) and Midazolam in Healthy Adult Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Midazolam First n=15 Participants Subjects received Midazolam 6mg in Period 1, followed by Midazolam 6mg and SSP-004184SS 30mg/kg during Period 2.	Midazolam + SSP-004184SS First n=15 Participants Subjects received Midazolam 6mg and SSP-004184SS 30mg/kg in Period 1, followed by Midazolam 6mg during Period 2.	Total n=30 Participants Total of all reporting groups
Age, Continuous	37 Years STANDARD_DEVIATION 10.45 • n=5 Participants	44.9 Years STANDARD_DEVIATION 10.53 • n=7 Participants	41 Years STANDARD_DEVIATION 11.07 • n=5 Participants
Age, Customized <=18 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Customized Between 18 and 65 years	14 Participants n=5 Participants	15 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment UNITED STATES	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: Study Periods 1 & 2: Within 60 minutes pre-dose, and Post-dose 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72 hours.

Population: Pharmacokinetic Set: All subjects who took at least 1 dose of investigational product and for whom the primary pharmacokinetic data were considered sufficient and interpretable.

AUCinf is the area under the plasma concentration versus time curve extrapolated from time 0 to infinity, calculated using the observed value of the last non-zero concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.

Outcome measures

Outcome measures
Measure	Midazolam n=29 Participants Administered as a single oral 6 mg dose on Day 1.	SSP-004184SS + Midazolam n=30 Participants Midazolam (6 mg) + SSP-004184SS (30 mg/kg) concomitantly administered as a single oral dose on Day 1.
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Midazolam	103.348 ng*hr/mL Standard Deviation 54.087	120.1 ng*hr/mL Standard Deviation 38.686

PRIMARY outcome

Timeframe: Study Periods 1 & 2: Within 60 minutes pre-dose, and Post-dose 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72 hours.

Population: Pharmacokinetic Set: All subjects who took at least 1 dose of investigational product and for whom the primary pharmacokinetic data were considered sufficient and interpretable.

AUClast is the area under the concentration versus time curve from the time of dosing to the last measurable concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.

Outcome measures

Outcome measures
Measure	Midazolam n=29 Participants Administered as a single oral 6 mg dose on Day 1.	SSP-004184SS + Midazolam n=30 Participants Midazolam (6 mg) + SSP-004184SS (30 mg/kg) concomitantly administered as a single oral dose on Day 1.
Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of Midazolam	100.935 ng*h/ml Standard Deviation 54.014	116.902 ng*h/ml Standard Deviation 37.45

PRIMARY outcome

Timeframe: Study Periods 1 & 2: Within 60 minutes pre-dose, and Post-dose 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72 hours.

Population: Pharmacokinetic Set: All subjects who took at least 1 dose of investigational product and for whom the primary pharmacokinetic data were considered sufficient and interpretable.

Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.

Outcome measures

Outcome measures
Measure	Midazolam n=29 Participants Administered as a single oral 6 mg dose on Day 1.	SSP-004184SS + Midazolam n=30 Participants Midazolam (6 mg) + SSP-004184SS (30 mg/kg) concomitantly administered as a single oral dose on Day 1.
Maximum Plasma Concentration (Cmax) of Midazolam	35.124 ng/mL Standard Deviation 12.532	48.29 ng/mL Standard Deviation 12.605

Adverse Events

Midazolam Alone

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Midazolam + SSP-004184SS

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Midazolam Alone n=29 participants at risk Administered as a single oral 20 mg dose on Day 1.	Midazolam + SSP-004184SS n=30 participants at risk Midazolam (6 mg) + SSP-004184SS (30 mg/kg) administered concomitantly as a single oral dose on Day 1.
Nervous system disorders Dizziness	6.9% 2/29 • Number of events 2	16.7% 5/30 • Number of events 5
Nervous system disorders Somnolence	13.8% 4/29 • Number of events 4	16.7% 5/30 • Number of events 5

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Publication restrictions are in place

Restriction type: OTHER