Relapsing-Remitting Multiple SclerosisPhase 3OBSERVENCT01462318

An Open-Label Immunogenicity and Pharmacokinetics Study of Daclizumab High Yield Process Prefilled Syringe in Relapsing Remitting Multiple Sclerosis

A Phase 3 study testing Midazolam, Caffeine and S-warfarin in people with Relapsing-Remitting Multiple Sclerosis, run by Biogen at 19 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Relapsing-Remitting Multiple Sclerosis
What is being tested?: Midazolam, Caffeine and S-warfarin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 133 participants
Where: 19 sitesin 4 countries
Study dates: Nov 2011to Jan 2016
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Must have a confirmed diagnosis of RRMS according to McDonald criteria and previous cranial magnetic resonance imaging demonstrating lesion(s) consistent with MS
Must have a baseline Expanded Disability Status Scale (EDSS) between 0.0 and 5.0, inclusive
Must have had 1 or more clinical relapses within the previous 2 years
Women of child bearing potential must be willing to practice effective contraception during the study and 4 months after the last dose
To be eligible for participation in the 3-year treatment extension, participants must meet the following eligibility criteria at the time of reinitiation of DAC HYP:
Must have been compliant with the 205MS302 (NCT01462318) protocol during the initial 24-week treatment period and the 20-week washout period in the opinion of the Investigator

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Must resume DAC HYP treatment ≤12 weeks after completion of the washout period (i.e., ≤12 weeks after their Week 44 visit).
Participants who are currently receiving an approved IFN ß preparation must discontinue interferon (IFN) ß treatment at the time of reinitiation of DAC HYP dosing (no washout is required).
To be eligible for participation in the TP-DI Sub-Study, subjects must meet the following eligibility criteria at the Screening Visit at Week 40:
Must have been compliant with the 205MS302 (NCT01462318) protocol during the initial 24-week treatment period and through Week 40 of the 20-week washout period in the opinion of the Investigator.
Must agree to resume DAC HYP treatment ≤12 weeks after completion of the washout period (i.e., ≤12 weeks after their Week 44 visit).
Must have normal liver function test results (total bilirubin ≤1.5 × upper limit of normal (ULN), alanine aminotransferase/aspartate aminotransferase ≤2 × ULN, and prothrombin time/partial thromboplastin time ≤1.2 × ULN).
Must have normal renal function as estimated creatinine clearance >60 mL/min (Cockcroft-Gault formula).
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Who cannot join

Other chronic disease of the immune system, malignancies, acute urologic, pulmonary, gastrointestinal disease
Female subjects who are currently pregnant or breastfeeding

Trial locations and contacts

19 sites in 4 countries.

Country

City, postcode or hospital

19 sites in 4 countries

United States7 sites

Research Site
Centennial, Colorado, 80112
Research Site
Dayton, Ohio, 45417
Research Site
Farmington Hills, Michigan, 48334
Research Site
Franklin, Tennessee, 37064
Research Site
Lake Barrington, Illinois, 60010
Research Site
Lexington, Kentucky, 40513
Research Site
Washington D.C., District of Columbia, 20057

Other trials in United States

Czechia5 sites

Research Site
Brno, 65691
Research Site
Jihlava, 58633
Research Site
Ostrava, 70852
Research Site
Pardubice, 53203
Research Site
Teplice, 41501

Other trials in Czechia

Hungary5 sites

Research Site
Budapest, 1134
Research Site
Debrecen, 4031
Research Site
Esztergom, 2500
Research Site
Székesfehérvár
Research Site
Veszprém, Korhazu 1, 8200

Other trials in Hungary

Poland2 sites

Research Site
Katowice
Research Site
Krakow, 31-501

Other trials in Poland

About this study

Official title: A Multicenter, Single-Arm, Open-Label Study to Evaluate the Immunogenicity and Pharmacokinetics of BIIB019, Daclizumab High Yield Process (DAC HYP), Prefilled Syringe Administered by Subcutaneous Injection in Subjects With Relapsing-Remitting Multiple Sclerosis

The primary objective of the study is to assess the immunogenicity of Daclizumab High Yield Process (DAC HYP) 150 mg administered every 4 weeks by subcutaneous (SC) injection using the pre-filled syringe (PFS) in participants with relapsing-remitting multiple sclerosis (RRMS). The secondary objectives of this study are to characterize the pharmacokinetics (PK) of DAC HYP following single and multiple doses of DAC HYP administered by the PFS in a subset of participants with RRMS and to evaluate the effect of DAC HYP on the PK of probe drugs for cytochrome P450 (CYP) isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A).

Read the detailed description

Following a screening period, participants will receive DAC HYP over a 24-week treatment period (6 monthly injections) and then enter a 20-week washout period for assessment of immunogenicity, PK, pharmacodynamics, safety, and tolerability. The 20-week washout is necessary to ensure measurement of anti-DAC HYP binding antibodies (ADAbs) and neutralizing antibodies (NAbs) in the absence of drug interference. After washout, the participants may resume monthly treatment with DAC HYP 150 mg for an additional 3 years. All participants will be followed for 6 months after their last dose for safety monitoring. Additionally, two sub-studies will be performed: (1) an intensive serial PK sampling performed over the first and last dosing interval following DAC HYP doses administered at week 0 and at week 20, and (2) a therapeutic protein-drug interaction (TP-DI) sub-study, during which a probe drug cocktail will be administered at weeks 43 and 53 followed by serial probe-drug PK sampling up to 96 hours after probe-drug administration. A maximum of 20 participants will be enrolled in the TP-DI sub-study.

Conditions: Relapsing-Remitting Multiple Sclerosis
Being tested: Midazolam, Caffeine, S-warfarin, Vitamin K, Omeprazole
Keywords: Pre-filled syringe, Pharmacokinetic, Daclizumab High Yield Process, immunogenicity
Medical subject headings: Multiple Sclerosis, Relapsing-Remitting

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MidazolamDrug
5 mg
CaffeineOther
200 mg
S-warfarinDrug
10 mg
Vitamin KOther
10 mg
OmeprazoleDrug
40 mg
DextromethorphanDrug
30 mg
BIIB019 (Daclizumab)Biological
Also called Daclizumab High Yield Process; DAC HYP
150 mg in 1 ml PFS

Study groups in NCT01462318
Study group	Role	What they receive
DAC HYP	Experimental	DAC HYP 150 mg by a subcutaneous (SC) injection using the pre-filled syringe (PFS) every 4 weeks for 24 weeks followed by a 20-week washout period. After completion of the washout period, participants may resume monthly DAC HYP 150 mg using the PFS for up to 3 additional years. Participants in the TP-DI sub-study will receive probe-drug cocktail administration at Weeks 43 and 53. The probe-drug cocktail consists of oral midazolam 5 mg, caffeine 200 mg, S-warfarin 10 mg, vitamin K 10 mg, omeprazole 40 mg, and dextromethorphan 30 mg. The oral vitamin K is used to counteract warfarin's anticoagula nt effect prophylactically. Receives: Drug: Midazolam; Other: Caffeine; Drug: S-warfarin; Other: Vitamin K; Drug: Omeprazole; Drug: Dextromethorphan; Biological: BIIB019 (Daclizumab)

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Anti-DAC HYP Binding Antibodies (ADAbs): Electrochemiluminescent (ECL) Anti-Drug Antibody (ADA) Assay
Participants with post-baseline (PB) ADAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose).
Measured: Up to 44 weeks
Number of Participants With Anti-DAC HYP Neutralizing Antibodies (NAbs): ECL ADA Assay
Participants with PB NAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose).
Measured: Up to 44 weeks
TP-DI Sub-study: Area-Under-the-Curve From Zero to Infinity (AUCinf) of Each Probe Drug
AUCinf of each of the following cytochrome P450 (CYP) isoenzyme substrates: midazolam (CYP3A), S-warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19). The AUC from zero to 12 hours (AUC0-12) was calculated for caffeine (CYP1A2).
Measured: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration
TP-DI Sub-study: Dextromethorphan to Dextrorphan Urine Concentration Ratio
Measured: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and for 12 hours after probe-drug cocktail administration

Secondary outcomes (10)

Intensive PK Sub-study: Cmax of DAC HYP
Measured: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14 and 21 days post-dose
Intensive PK Sub-study: Time to Reach Maximum Concentration (Tmax) of DAC HYP
Measured: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14 and 21 days post-dose
Intensive PK Sub-study: Area-Under-the-Curve From Start to End of the Dosing Interval (AUCtau) of DAC HYP
Measured: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14, and 21 days post-dose
Intensive PK Sub-study: Minimum Concentrations (Cmin) of DAC HYP
Measured: Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose
Intensive PK Sub-study: Apparent Volume of Distribution (V/F) of DAC HYP
Measured: Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose
Intensive PK Sub-study: Elimination Half-life (t½) of DAC HYP
Measured: Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose
Intensive PK Sub-study: Apparent Clearance (CL/F) of DAC HYP
Measured: Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose
TP-DI Sub-study: Cmax of Each Probe Drug
Cmax of each of the following CYP isoenzyme substrates: midazolam (CYP3A), caffeine (CYP1A2), warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19).
Measured: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration
TP-DI Sub-study: CL/F of Each Probe Drug
CL/F of each of the following CYP isoenzyme substrates: midazolam (CYP3A), warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19).
Measured: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration
TP-DI Sub-study: Omeprazole/Hydroxyomeprazole Concentration Ratio at 2 Hours Post-omeprazole Dosing
Measured: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration) at 2 hours after probe drug cocktail administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2011Jan 2016

First posted31 Oct 2011 (estimated)
Study startNov 2011
Primary completionJan 2016
Study completionJan 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Relapsing-Remitting Multiple SclerosisStudies of the same condition, open and under way.
More trials run by BiogenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 133 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01462318
Sponsor's protocol ID: 205MS302
Other IDs: 2010-023856-97
Acronym: OBSERVE
Status last verified: Jan 2017
First submitted: 14 Jul 2011
Last updated: 14 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Gold R, Stefoski D, Selmaj K, Havrdova E, Hurst C, Holman J, Tornesi B, Akella S, McCroskery P. Pregnancy Experience: Nonclinical Studies and Pregnancy Outcomes in the Daclizumab Clinical Study Program. Neurol Ther. 2016 Dec;5(2):169-182. doi: 10.1007/s40120-016-0048-2. Epub 2016 Jul 13.
PubMed 27411694

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 14 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Single-Arm, Open-Label Study to Evaluate the Immunogenicity and Pharmacokinetics of BIIB019, Daclizumab High Yield Process (DAC HYP), Prefilled Syringe Administered by Subcutaneous Injection in Subjects With Relapsing-Remitting Multiple Sclerosis
ClinicalTrials.gov ID: NCT01462318
Acronym / sponsor ID: OBSERVE / 205MS302
Conditions: Relapsing-Remitting Multiple Sclerosis
Keywords: Pre-filled syringe, Pharmacokinetic, Daclizumab High Yield Process, immunogenicity
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 133 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Study start: Nov 2011
Primary completion: Jan 2016 (actual)
Study completion: Jan 2016 (actual)
First posted: 31 Oct 2011 (estimated)
Results: Posted 14 Mar 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
DAC HYP	Experimental	Drug: Midazolam, Other: Caffeine, Drug: S-warfarin, Other: Vitamin K, Drug: Omeprazole, Drug: Dextromethorphan, Biological: BIIB019 (Daclizumab)DAC HYP 150 mg by a subcutaneous (SC) injection using the pre-filled syringe (PFS) every 4 weeks for 24 weeks followed by a 20-week washout period. After completion of the washout period, participants may resume monthly DAC HYP 150 mg using the PFS for up to 3 additional years. Participants in the TP-DI sub-study will receive probe-drug cocktail administration at Weeks 43 and 53. The probe-drug cocktail consists of oral midazolam 5 mg, caffeine 200 mg, S-warfarin 10 mg, vitamin K 10 mg, omeprazole 40 mg, and dextromethorphan 30 mg. The oral vitamin K is used to counteract warfarin's anticoagula nt effect prophylactically.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Must have a confirmed diagnosis of RRMS according to McDonald criteria and previous cranial magnetic resonance imaging demonstrating lesion(s) consistent with MS
Must have a baseline Expanded Disability Status Scale (EDSS) between 0.0 and 5.0, inclusive
Must have had 1 or more clinical relapses within the previous 2 years
Women of child bearing potential must be willing to practice effective contraception during the study and 4 months after the last dose
To be eligible for participation in the 3-year treatment extension, participants must meet the following eligibility criteria at the time of reinitiation of DAC HYP:

Key exclusion criteria (2 listed)

Other chronic disease of the immune system, malignancies, acute urologic, pulmonary, gastrointestinal disease
Female subjects who are currently pregnant or breastfeeding

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Midazolam5 mg	Drug	DAC HYP
Caffeine200 mg	Other	DAC HYP
S-warfarin10 mg	Drug	DAC HYP
Vitamin K10 mg	Other	DAC HYP
Omeprazole40 mg	Drug	DAC HYP
Dextromethorphan30 mg	Drug	DAC HYP
BIIB019 (Daclizumab)Also: Daclizumab High Yield Process; DAC HYP150 mg in 1 ml PFS	Biological	DAC HYP

Primary outcome

Number of Participants With Anti-DAC HYP Binding Antibodies (ADAbs): Electrochemiluminescent (ECL) Anti-Drug Antibody (ADA) Assay
Time frame: Up to 44 weeks
Participants with post-baseline (PB) ADAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose).
Number of Participants With Anti-DAC HYP Neutralizing Antibodies (NAbs): ECL ADA Assay
Time frame: Up to 44 weeks
Participants with PB NAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose).
TP-DI Sub-study: Area-Under-the-Curve From Zero to Infinity (AUCinf) of Each Probe Drug
Time frame: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration
AUCinf of each of the following cytochrome P450 (CYP) isoenzyme substrates: midazolam (CYP3A), S-warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19). The AUC from zero to 12 hours (AUC0-12) was calculated for caffeine (CYP1A2).
TP-DI Sub-study: Dextromethorphan to Dextrorphan Urine Concentration Ratio
Time frame: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and for 12 hours after probe-drug cocktail administration

10 secondary outcomes

Intensive PK Sub-study: Cmax of DAC HYP
Time frame: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14 and 21 days post-dose
Intensive PK Sub-study: Time to Reach Maximum Concentration (Tmax) of DAC HYP
Time frame: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14 and 21 days post-dose
Intensive PK Sub-study: Area-Under-the-Curve From Start to End of the Dosing Interval (AUCtau) of DAC HYP
Time frame: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14, and 21 days post-dose
Intensive PK Sub-study: Minimum Concentrations (Cmin) of DAC HYP
Time frame: Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose
Intensive PK Sub-study: Apparent Volume of Distribution (V/F) of DAC HYP
Time frame: Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose
Intensive PK Sub-study: Elimination Half-life (t½) of DAC HYP
Time frame: Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose
Intensive PK Sub-study: Apparent Clearance (CL/F) of DAC HYP
Time frame: Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose
TP-DI Sub-study: Cmax of Each Probe Drug
Time frame: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration
TP-DI Sub-study: CL/F of Each Probe Drug
Time frame: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration
TP-DI Sub-study: Omeprazole/Hydroxyomeprazole Concentration Ratio at 2 Hours Post-omeprazole Dosing
Time frame: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration) at 2 hours after probe drug cocktail administration

Results and safety

Results posted to the registry on 14 Mar 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Main Study	113	105
Therapeutic Protein-Drug Interaction (TP-DI)Sub-study	20	20
Extension Phase	0	0

Primary outcome: Number of Participants With Anti-DAC HYP Binding Antibodies (ADAbs): Electrochemiluminescent (ECL) Anti-Drug Antibody (ADA) Assay

Time frame: Up to 44 weeks. Number. Unit: participants

Measure	Main Study n = 113
PB ADAbs through Week 44=negative; n=113	78
PB ADAbs through Week 44=positive; n=113	35
PB ADAbs in treatment period=negative; n=113	92
PB ADAbs in treatment period=positive; n=113	21
PB ADAbs in post-treatment period=negative; n=110	89
PB ADAbs in post-treatment period=positive; n=110	21

Population analysed: Immunogenicity evaluable population: all participants in the main study population who received at least 1 dose of DAC HYP and had at least 1 post-study baseline immunogenicity assessment; n=participants with an assessment during the given period.

Primary outcome: Number of Participants With Anti-DAC HYP Neutralizing Antibodies (NAbs): ECL ADA Assay

Time frame: Up to 44 weeks. Number. Unit: participants

Measure	Main Study n = 113
PB NAbs through Week 44=negative; n=113	105
PB NAbs through Week 44=positive; n=113	8
PB NAbs in treatment period=negative; n=113	109
PB NAbs in treatment period=positive; n=113	4
PB NAbs in post-treatment period=negative; n=110	104
PB NAbs in post-treatment period=positive; n=110	6

Primary outcome: TP-DI Sub-study: Area-Under-the-Curve From Zero to Infinity (AUCinf) of Each Probe Drug

Time frame: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration. Mean (Standard Deviation). Unit: hr*ng/mL

Measure	TP-DI Sub-study n = 20
Midazolam (Period 1) AUCinf; n=20	786.75 (328.794)
Midazolam+DAC HYP (Period 2) AUCinf; n=19	816.87 (403.958)
S-warfarin (Period 1) AUCinf; n=17	19292.9 (5524.60)
S-warfarin+DAC HYP (Period 2) AUCinf; n=18	19609.3 (4620.64)
Omeprazole (Period 1) AUCinf; n=18	2214.5 (2622.15)
Omeprazole+DAC HYP (Period 2) AUCinf; n=19	1770.0 (1673.80)
Caffeine (Period 1) AUC0-12; n=20	35742.4 (13942.71)
Caffeine+DAC HYP (Period 2) AUC0-12; n=20	37449.2 (14367.04)

TP-DI Sub-study: ratio: 1.015 (90% CI 0.894 to 1.153)
TP-DI Sub-study: ratio: 1.005 (90% CI 0.951 to 1.063)
TP-DI Sub-study: ratio: 0.996 (90% CI 0.880 to 1.127)

Population analysed: TP-DI Sub-study population: all participants in the TP-DI substudy who had enough post-baseline measurable drug concentrations to calculate the parameter; n=participants with an evaluable assessment at given time point.

Primary outcome: TP-DI Sub-study: Dextromethorphan to Dextrorphan Urine Concentration Ratio

Time frame: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and for 12 hours after probe-drug cocktail administration. Mean (Standard Deviation). Unit: ratio

Measure	TP-DI Sub-study n = 20
Dextromethorphan (Period 1)	0.42468 (1.258565)
Dextromethorphan+DAC HYP (Period 2)	0.48939 (1.813077)

TP-DI Sub-study: ratio: 1.012 (90% CI 0.764 to 1.342)

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Screening (for serious adverse events) or first dose of study treatment on Day 1 (for adverse events) through the end of treatment. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
DAC HYP 150 mg	33 of 133 (24.8%)	106 of 133 (79.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 27411694Gold R, Stefoski D, Selmaj K, Havrdova E, Hurst C, Holman J, Tornesi B, Akella S, McCroskery P. Pregnancy Experience: Nonclinical Studies and Pregnancy Outcomes in the Daclizumab Clinical Study Program. Neurol Ther. 2016 Dec;5(2):169-182. doi: 10.1007/s40120-016-0048-2. Epub 2016 Jul 13.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Biogen

19 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Midazolam, Caffeine and S-warfarin in people with Relapsing-Remitting Multiple Sclerosis, run by Biogen at 19 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Czechia, Hungary, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Anti-DAC HYP Binding Antibodies (ADAbs): Electrochemiluminescent (ECL) Anti-Drug Antibody (ADA) Assay (time frame: Up to 44 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01462318, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2017.