Trial Outcomes & Findings for Effect of Ketoconazole on Sufentanil NanoTab Pharmacokinetics (NCT NCT01721070)

NCT ID: NCT01721070

Last Updated: 2016-11-04

Results Overview

Total amount of sufentanil absorbed; After each dosing of Sufentanil NanoTab, serial blood samples will be taken at regular time points.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 19 participants
• Primary outcome timeframe: 0 (pre-dose), 10, 20, 30, 40, 50, 60, 70, 80, 90, 120, 180, 240, 360, 480, 600, 720, and 840 minutes, and 24 hours after dosing.24 hours
• Results posted on: 2016-11-04

Participant Flow

Participant milestones

Measure	SUF NT 15 mcg Followed by Ketoconazole 400 mg + SUF NT 15 mcg Period 1: One SUF NT 15 mcg administered sublingually followed by Period 2. Period 2: Ketoconazole 400 mg given daily for three days; One SUF NT 15 mcg was also co-administered sublingually with the third (last) ketoconazole dose. Subjects also received one dose of oral naltrexone 50 mg in the evening before and the morning of each SUF NT 15 mcg dosing to block the opioid effects of the sufentanil.
SUF NT 15 mcg STARTED	19
SUF NT 15 mcg COMPLETED	19
SUF NT 15 mcg NOT COMPLETED	0
Ketoconazole 400 mg and SUF NT 15 mcg STARTED	19
Ketoconazole 400 mg and SUF NT 15 mcg COMPLETED	18
Ketoconazole 400 mg and SUF NT 15 mcg NOT COMPLETED	1

Reasons for withdrawal

Measure

SUF NT 15 mcg Followed by Ketoconazole 400 mg + SUF NT 15 mcg Period 1: One SUF NT 15 mcg administered sublingually followed by Period 2. Period 2: Ketoconazole 400 mg given daily for three days; One SUF NT 15 mcg was also co-administered sublingually with the third (last) ketoconazole dose. Subjects also received one dose of oral naltrexone 50 mg in the evening before and the morning of each SUF NT 15 mcg dosing to block the opioid effects of the sufentanil.

Ketoconazole 400 mg and SUF NT 15 mcg Withdrawal by Subject

1

Baseline Characteristics

Effect of Ketoconazole on Sufentanil NanoTab Pharmacokinetics

Baseline characteristics by cohort

Measure	SUF NT 15 mcg Then 3 Days of Ketoconazole and SUF NT 15 mcg n=19 Participants Period 1: SUF NT 15 mcg administered once sublingually. Subjects also received one dose of oral naltrexone 50 mg in the evening before and the morning of each SUF NT dosing to block the opioid effects of the sufentanil. Period 2: Ketoconazole 400 mg given daily for three days. One SUF NT 15 mcg was also co-administered sublingually with the third (last) ketoconazole dose. Subjects also received one dose of oral naltrexone 50 mg in the evening before and the morning of each SUF NT dosing to block the opioid effects of the sufentanil.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants

PRIMARY outcome

Timeframe: 0 (pre-dose), 10, 20, 30, 40, 50, 60, 70, 80, 90, 120, 180, 240, 360, 480, 600, 720, and 840 minutes, and 24 hours after dosing.24 hours

Population: 2 of the 19 subjects had incomplete PK data and were excluded from PK analysis (1 due to early withdrawal and 1 due to AE)

Total amount of sufentanil absorbed; After each dosing of Sufentanil NanoTab, serial blood samples will be taken at regular time points.

Outcome measures

Measure	SUF NT 15 mcg n=17 Participants One SUF NT 15 mcg administered sublingually. Subjects also received one dose of oral naltrexone 50 mg in the evening before and the morning of each SUF NT dosing to block the opioid effects of the sufentanil.	Ketoconazole 400 mg and SUF NT 15 mcg n=17 Participants Ketoconazole 400 mg given orally daily for three days. One SUF NT 15 mcg is also co-administered sublingually with the third (last) ketoconazole dose. Subjects also received one dose of oral naltrexone 50 mg in the evening before and the morning of each SUF NT dosing to block the opioid effects of the sufentanil.
AUC (0-inf)	126.47 h*pg/mL Geometric Coefficient of Variation 46.42	223.63 h*pg/mL Geometric Coefficient of Variation 45.45

PRIMARY outcome

Timeframe: 0 (pre-dose), 10, 20, 30, 40, 50, 60, 70, 80, 90, 120, 180, 240, 360, 480, 600, 720, and 840 minutes, and 24 hours after dosing.

Population: 2 of the 19 subjects had incomplete PK data and were excluded from PK analysis (1 due to early withdrawal and 1 due to AE)

Maximum plasma concentration; After each dosing of Sufentanil NanoTab, serial blood samples will be taken at regular time points.

Outcome measures

Measure	SUF NT 15 mcg n=17 Participants One SUF NT 15 mcg administered sublingually. Subjects also received one dose of oral naltrexone 50 mg in the evening before and the morning of each SUF NT dosing to block the opioid effects of the sufentanil.	Ketoconazole 400 mg and SUF NT 15 mcg n=17 Participants Ketoconazole 400 mg given orally daily for three days. One SUF NT 15 mcg is also co-administered sublingually with the third (last) ketoconazole dose. Subjects also received one dose of oral naltrexone 50 mg in the evening before and the morning of each SUF NT dosing to block the opioid effects of the sufentanil.
Cmax	39.95 pg/mL Standard Deviation 18.57	46.00 pg/mL Standard Deviation 16.50

Adverse Events

SUF NT 15 mcg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Ketoconazole 400 mg + SUF NT 15 mcg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	SUF NT 15 mcg n=19 participants at risk One SUF NT 15 mcg administered sublingually. Subjects also received one dose of oral naltrexone 50 mg in the evening before and the morning of each SUF NT dosing to block the opioid effects of the sufentanil.	Ketoconazole 400 mg + SUF NT 15 mcg n=18 participants at risk Ketoconazole 400 mg given daily for three days. One SUF NT 15 mcg was also co-administered sublingually with the third (last) ketoconazole dose. Subjects also received one dose of oral naltrexone 50 mg in the evening before and the morning of each SUF NT dosing to block the opioid effects of the sufentanil.
Gastrointestinal disorders Nausea	5.3% 1/19 • Four days	5.6% 1/18 • Four days
Gastrointestinal disorders Abdominal Discomfort	5.3% 1/19 • Four days	11.1% 2/18 • Four days
Gastrointestinal disorders Constipation	5.3% 1/19 • Four days	0.00% 0/18 • Four days
Gastrointestinal disorders Dyspepsia	0.00% 0/19 • Four days	5.6% 1/18 • Four days
Infections and infestations Viral Upper Respiratory Tract Infection	5.3% 1/19 • Four days	0.00% 0/18 • Four days
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/19 • Four days	5.6% 1/18 • Four days
Nervous system disorders Headache	5.3% 1/19 • Four days	5.6% 1/18 • Four days
Nervous system disorders Lethargy	5.3% 1/19 • Four days	0.00% 0/18 • Four days
Vascular disorders Hot Flush	5.3% 1/19 • Four days	5.6% 1/18 • Four days
Eye disorders Photophobia	0.00% 0/19 • Four days	5.6% 1/18 • Four days

Additional Information

Pamela Palmer, MD, PhD

AcelRx Pharmaceuticals, Inc.

Phone: 650-216-3504

Email: ppalmer@acelrx.com

Results disclosure agreements

• Principal investigator is a sponsor employee Requires prior approval from AcelRx Pharmaceuticals, Inc.
• Publication restrictions are in place

Restriction type: OTHER